Atlas Journal

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Atlas Journal

Atlas Journal versus Atlas Database: the accumulation of the issues of the Journal constitutes the body of the Database/Text-Book. TABLE OF CONTENTS Volume 2, Number 2, Apr-Jun 1998 Previous Issue / Next Issue Genes FGFR1 (Fibroblast Growth Factor Receptor 1) (8p12). Jean-Loup Huret. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 117-125. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Genes/FGFR1113.html LCP1 (lymphocyte cytosolic protein1) (13q14). Sylvie Galiègue-Zouitina. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 126-130. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Genes/LCP1ID95.html MTCP1 (Mature T Cell Proliferation 1) (Xq28). Marc-Henri Stern. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 131-136. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Genes/MTCP1ID89.html NF2 (neurofibromatosis type 2) (22q12.1-12.2) - updated. Jean-Loup Huret. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 137-143. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Genes/NF2117.html MYCN (myc myelocytomatosis viral related oncogene, neuroblastoma derived) (2p24.1). Jean-Loup Huret. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 144-148. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Genes/NMYC112.html POU2AF1 (POU domain, class 2, associating factor 1) (11q23.1). Sylvie Galiègue-Zouitina. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 149-153. [Full Text] [PDF]

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) I URL : http://AtlasGeneticsOncology.org/Genes/OBF94.html ABCB1 (7q21.2). Franck Viguié. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 154-160. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Genes/PGY1ID105.html TAL1 (T-cell acute leukemia 1) (1p32) - updated. Jean-Loup Huret, Marie Claude Labastie. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 161-165. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Genes/TAL1.html TCL1A (T-cell leukemia/lymphoma 1A) (14q32.1). Marc-Henri Stern. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 166-170. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Genes/TCL1ID66.html TCTA (T-cell leukemia translocation-associated gene) (3p21) - updated. Jean-Loup Huret. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 171-174. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Genes/TCTA.html FIM (fused in myeloproliferative disorders) (13q12). Jean-Loup Huret, Dominique Leroux. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 175-180. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Genes/ZNF198ID114.html Leukaemias t(9;12)(p24;p13). Jean-Loup Huret. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 181-182. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Anomalies/1122t0912.html del(9q) solely. Franck Viguié. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 183-187. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Anomalies/del9q.html Essential thrombocythemia; Idiopathic thrombocythemia - updated. Jean-Loup Huret. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 188-189. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Anomalies/ET.html Acute basophilic leukemia; t(X;6)(p11;q23). Nicole Dastugue. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 190-191. [Full Text] [PDF]

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) II URL : http://AtlasGeneticsOncology.org/Anomalies/LAbaso1124.html t(5;14)(q33;q32) PDGFRB/TRIP11. Jean-Loup Huret. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 192-193. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Anomalies/t0514ANL.html t(11;16)(q23;p13). Jean-Loup Huret. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 194-196. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Anomalies/t1116.html t(16;21)(p11;q22). Christine Pérot. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 197-203. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Anomalies/t1621.html Solid Tumours Nervous system tumors: Neuroblastoma. Jérome Couturier, Daniel Satgé. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 204-208. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Tumors/neurob5002.html t(16;21)(p11;q22) in Ewing's tumours. Christine Pérot. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 209-214. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Tumors/t1621p11q22EwingID5329.html Cancer Prone Diseases Bannayan-Riley-Ruvalcaba syndrome. Jean-Loup Huret. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 215-218. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Kprones/BannayanID10044.html Bloom syndrome. Jean-Loup Huret. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 219-228. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Kprones/BLO10002.html Dubowitz syndrome. Jean-Loup Huret, Claude Léonard. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 229-230. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Kprones/DUB10016.html Fanconi anaemia.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) III Jean-Loup Huret. Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2): 231-237. [Full Text] [PDF] URL : http://AtlasGeneticsOncology.org/Kprones/FA10001.html Deep Insights Case Reports Educational Items

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Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) IV Atlas of Genetics and Cytogenetics in Oncology and Haematology

FGFR1 (Fibroblast Growth Factor Receptor 1) (updated: old version not available)

Identity Other BFGFR (basic fibroblast growth factor receptor) names FLT2 (FMS-like tyrosine kinase 2) FLG (FMS-like gene) CEK FGFBR N-SAM Hugo FGFR1 Location 8p12

FGFR1 (8p12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact [email protected]

DNA/RNA Transcription 2.7 mRNA Protein

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 117 -

Protein Diagram

Description 822 amino acids; 100-135 kDa glycoprotein from a 90-115 kDa protein core; tyrosine kinase receptor; contains four major domains: an extracellular domain with 2 or 3 Ig-like loops, a transmembrane domain and an intracellular domain , a juxtamembrane domain, and an intracellular domain composed of the tyrosine kinase domain (two kinase domains interrupted by a short kinase insert), and a C-terminal tail. Localisation plasma membrane Function FGF receptor with tyrosine kinase activity; binding of ligand (FGF)) in association with heparan sulfate proteoglycans induces receptor dimerization, autophosphorylation and signal transduction Homology with other FGFR (FGFR2, FGFR3, and FGFR4) Implicated in Entity stem-cell myeloproliferative disorder associated with chromosomal translocations involving 8p12; to date, seven FGFR1 partners have been described (see below) Disease stem-cell myeloproliferative disorder characterized by T- or B-cell lymphoblastic leukemia/lymphoma, myeloid hyperplasia, and peripheral blood eosinophilia, and it generally progresses to acute myeloid leukemia; specific to the 8p12 chromosomal region Prognosis very poor (median survival: 12 mths)

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 118 - Cytogenetics the 7 translocations are: t(6;8)(q27; p12) involving FOP (FGFR1 Oncogene Partner) t(8;9)(p12;q33) involving CEP110 (Centrosome protein 110) t(8;11)(p12;p15) t(8;12)(p12;q15) t(8;13)(p12;q12 ) involving FIM (Fused In Myeloproliferative disorder also called ZNF198 or RAMP) t(8;17)(p12;q25) t(8;19)(p12;q13.3) additional anomalies: in the t(8;9)(p12;q33): +der(9), +21; in the t(8;13)(p12;q12): +8, +der(13), +21

Hybrid/Mutated 5' FOP - 3' FGFR1 in the t(6;8) Gene 5'CEP110 - FGFR1 in the t(8;9) 5' FIM/ZNF198 - 3' FGFR1 in the t(8;13) Abnormal three fusion transcripts are identified: FOP-FGFR1, CEP110-FGFR1, and Protein FIM-FGFR1; they encode large proteins containing the N-term of either FOP or CEP110, or FIM, and the catalytic domain of FGFR1 at their C- term: N-term leucine-rich region from FOP fused to the catalytic domain of FGFR1 N-term leucine zipper motifs from CEP110 fused to the catalytic domain of FGFR1 N-term zinc fingers from FIM fused to the Tyrosine kinase domain of FGFR1in C-term Oncogenesis constitutive activation of FGFR1

Entity Pfeiffer syndrome (inborn disease) Disease one form of Pfeiffer syndrome, an autosomal dominant craniosynostosis

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 119 - syndrome with broad thumbs and usually no mental deficiency, is due to a mutation in amino acid 252 (Pro252Arg substitution) of FGFR1

Entity Breast cancer Disease gene amplification and overexpression in sporadic breast tumors

Breakpoints

External links Nomenclature Hugo FGFR1 GDB FGFR1 FGFR1 2260 fibroblast growth factor receptor 1 (fms-related tyrosine Entrez_Gene kinase 2, Pfeiffer syndrome) Cards Atlas FGFR1113 GeneCards FGFR1 Ensembl FGFR1 CancerGene FGFR1 Genatlas FGFR1 GeneLynx FGFR1 eGenome FGFR1 euGene 2260

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 120 - Genomic and cartography GoldenPath FGFR1 - 8p12 chr8:38389449-38445293 - 8p12 (hg17-May_2004) Ensembl FGFR1 - 8p12 [CytoView]

NCBI Genes Cyto Gene Seq [Map View - NCBI] OMIM Disease map [OMIM] HomoloGene FGFR1 Gene and transcription

Genbank A29216 [ SRS ] A29216 [ ENTREZ ]

Genbank AY585209 [ SRS ] AY585209 [ ENTREZ ]

Genbank AK024388 [ SRS ] AK024388 [ ENTREZ ]

Genbank BC015035 [ SRS ] BC015035 [ ENTREZ ]

Genbank BC018128 [ SRS ] BC018128 [ ENTREZ ]

RefSeq NM_000604 [ SRS ] NM_000604 [ ENTREZ ]

RefSeq NM_015850 [ SRS ] NM_015850 [ ENTREZ ]

RefSeq NM_023105 [ SRS ] NM_023105 [ ENTREZ ]

RefSeq NM_023106 [ SRS ] NM_023106 [ ENTREZ ]

RefSeq NM_023107 [ SRS ] NM_023107 [ ENTREZ ]

RefSeq NM_023108 [ SRS ] NM_023108 [ ENTREZ ]

RefSeq NM_023109 [ SRS ] NM_023109 [ ENTREZ ]

RefSeq NM_023110 [ SRS ] NM_023110 [ ENTREZ ]

RefSeq NM_023111 [ SRS ] NM_023111 [ ENTREZ ]

RefSeq NT_086740 [ SRS ] NT_086740 [ ENTREZ ] AceView FGFR1 AceView - NCBI TRASER FGFR1 Traser - Stanford

Unigene Hs.549034 [ SRS ] Hs.549034 [ NCBI ] HS549034 [ spliceNest ] Protein : pattern, domain, 3D structure

SwissProt P11362 [ SRS] P11362 [ EXPASY ] P11362 [ INTERPRO ]

Prosite PS50835 IG_LIKE [ SRS ] PS50835 IG_LIKE [ Expasy ]

PS00107 PROTEIN_KINASE_ATP [ SRS ] PS00107 Prosite PROTEIN_KINASE_ATP [ Expasy ]

PS50011 PROTEIN_KINASE_DOM [ SRS ] PS50011 Prosite PROTEIN_KINASE_DOM [ Expasy ]

PS00109 PROTEIN_KINASE_TYR [ SRS ] PS00109 Prosite PROTEIN_KINASE_TYR [ Expasy ]

Interpro IPR007110 Ig-like [ SRS ] IPR007110 Ig-like [ EBI ]

Interpro IPR011009 Kinase_like [ SRS ] IPR011009 Kinase_like [ EBI ]

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 121 - Interpro IPR000719 Prot_kinase [ SRS ] IPR000719 Prot_kinase [ EBI ]

Interpro IPR001245 Tyr_pkinase [ SRS ] IPR001245 Tyr_pkinase [ EBI ]

Interpro IPR008266 Tyr_pkinase_AS [ SRS ] IPR008266 Tyr_pkinase_AS [ EBI ] CluSTr P11362

Pfam PF00047 ig [ SRS ] PF00047 ig [ Sanger ] pfam00047 [ NCBI-CDD ] Pfam PF00069 Pkinase [ SRS ] PF00069 Pkinase [ Sanger ] pfam00069 [ NCBI-CDD ]

Prodom PD000001 Prot_kinase[INRA-Toulouse] Prodom P11362 FGR1_HUMAN [ Domain structure ] P11362 FGR1_HUMAN [ sequences sharing at least 1 domain ] Blocks P11362

PDB 1AGW [ SRS ] 1AGW [ PdbSum ], 1AGW [ IMB ]

PDB 1CVS [ SRS ] 1CVS [ PdbSum ], 1CVS [ IMB ]

PDB 1EVT [ SRS ] 1EVT [ PdbSum ], 1EVT [ IMB ]

PDB 1FGI [ SRS ] 1FGI [ PdbSum ], 1FGI [ IMB ]

PDB 1FGK [ SRS ] 1FGK [ PdbSum ], 1FGK [ IMB ]

PDB 1FQ9 [ SRS ] 1FQ9 [ PdbSum ], 1FQ9 [ IMB ]

PDB 2FGI [ SRS ] 2FGI [ PdbSum ], 2FGI [ IMB ] Polymorphism : SNP, mutations, diseases OMIM 136350 [ map ] GENECLINICS 136350

SNP FGFR1 [dbSNP-NCBI]

SNP NM_000604 [SNP-NCI]

SNP NM_015850 [SNP-NCI]

SNP NM_023105 [SNP-NCI]

SNP NM_023106 [SNP-NCI]

SNP NM_023107 [SNP-NCI]

SNP NM_023108 [SNP-NCI]

SNP NM_023109 [SNP-NCI]

SNP NM_023110 [SNP-NCI]

SNP NM_023111 [SNP-NCI]

SNP FGFR1 [GeneSNPs - Utah] FGFR1 [SNP - CSHL] FGFR1] [HGBASE - SRS] General knowledge Family FGFR1 [UCSC Family Browser] Browser SOURCE NM_000604

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 122 - SOURCE NM_015850 SOURCE NM_023105 SOURCE NM_023106 SOURCE NM_023107 SOURCE NM_023108 SOURCE NM_023109 SOURCE NM_023110 SOURCE NM_023111 SMD Hs.549034 SAGE Hs.549034 Enzyme 2.7.1.112 [ Enzyme-SRS ] 2.7.1.112 [ Brenda-SRS ] 2.7.1.112 [ KEGG ] 2.7.1.112 [ WIT ] Amigo function|ATP binding Amigo process|MAPKKK cascade Amigo function|fibroblast growth factor receptor activity Amigo process|fibroblast growth factor receptor signaling pathway Amigo function|heparin binding Amigo component|integral to plasma membrane Amigo process|protein amino acid phosphorylation Amigo process|protein amino acid phosphorylation Amigo function|protein serine/threonine kinase activity Amigo function|protein-tyrosine kinase activity Amigo function|protein-tyrosine kinase activity Amigo function|receptor activity Amigo process|skeletal development Amigo function|transferase activity PubGene FGFR1 Other databases Probes Probe Cancer Cytogenetics (Bari) Probe FGFR1 Related clones (RZPD - Berlin) PubMed PubMed 48 Pubmed reference(s) in LocusLink Bibliography Purification and complementary DNA cloning of a receptor for basic fibroblast growth factor.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 123 - Lee PL, Johnson DE, Cousens LS, Fried VA, Williams LT. Science 1989; 245: 57-60. Medline 89298406

The complete amino acid sequence of the shorter form of human basic fibroblast growth factor receptor deduced from its cDNA. Itoh N, Terachi T, Ohta M, Seo MK. Biochem Biophys Res Commun 1990;169: 680-685. Medline 90290512

The human fibroblast growth factor receptor genes: a common structural arrangement underlies the mechanisms for generating receptor forms that differ in their third immunoglobulin domain. Johnson DE, Lu J, Chen H, Werner S, Williams LT. Mol Cell Biol 1991; 11: 4627-4634. Medline 91342665 cDNA cloning and expression of a human FGF receptor which binds acidic and basic FGF. Wennstrom S, Sandstrom C, Claesson-Welsh L. Growth Factors 1991; 4: 197-208. Medline 92118394

Structural and functional diversity in the FGF receptor multigene family. Johnson DE, Williams LT. Adv Cancer Res 1993; 60:1-41.

FGFR activation in skeletal disorders: too much of a good thing. Webster MK, Donoghue DJ. Trends Genet 1997; 13: 178-182. Medline 97298558

Differential expression assay of chromosome arm 8p genes identifies Frizzled- related (FRP1/FRZB) and Fibroblast Growth Factor Receptor 1 (FGFR1) as candidate breast cancer genes. Ugolini F, AdŽla•de J, Charafe-Jauffret E, Nguyen C, Jacquemier J, Jordan B, Birnbaum D, PŽbusque MJ. Oncogene 1999; 18: 1903-1910.

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Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 124 - BiblioGene - INIST

Contributor(s) Written 03-1998 Jean-Loup Huret Updated 12-2000 Marie-Josèphe Pébusque Citation This paper should be referenced as such : Huret JL . FGFR1 (Fibroblast Growth Factor Receptor 1). Atlas Genet Cytogenet Oncol Haematol. March 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/FGFR1113.html Pébusque MJ . FGFR1 (Fibroblast Growth Factor Receptor 1). Atlas Genet Cytogenet Oncol Haematol. December 2000 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/FGFR1113.html

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 125 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

LCP1 (lymphocyte cytosolic protein1)

Identity Other L-Plastine names Hugo LCP1 Location 13q14 DNA/RNA Description spans on a 90 kb genomic fragment; 16 exons, large first intron (20kb) Transcription 3.7 kb mRNA; coding sequence from exon 2 to exon 16: 3500 bp Protein

Description 570 amino acids Expression restricted to the hematopoietic cells (leukocytes); expression induced in all tumor cells of all tissues Localisation membrane Homology belongs to an actin-binding protein family (T-Plastin, Fimbrin, I-Plastin) Implicated in Entity t(3;13)(q27;q14)/ NHL --> LCP1 - BCL6 Disease non Hodgkin follicular as well as Burkitt lymphomas Cytogenetics t(3;13) is observed as a secondary anomaly Hybrid/Mutated both 5' L-Plastin- 3' BCL6 and 5' BCL6 - 3' L-Plastin, leading to two Gene fusion transcripts Abnormal no fusion protein, but promoter exchange between both partner genes Protein

External links Nomenclature Hugo LCP1 GDB LCP1 Entrez_Gene LCP1 3936 lymphocyte cytosolic protein 1 (L-plastin)

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 126 - Cards Atlas LCP1ID95 GeneCards LCP1 Ensembl LCP1 CancerGene LCP1 Genatlas LCP1 GeneLynx LCP1 eGenome LCP1 euGene 3936 Genomic and cartography LCP1 - 13q14 chr13:45598060-45654395 - 13q14.13 (hg17- GoldenPath May_2004) Ensembl LCP1 - 13q14.13 [CytoView]

NCBI Genes Cyto Gene Seq [Map View - NCBI] OMIM Disease map [OMIM] HomoloGene LCP1 Gene and transcription

Genbank AL137141 [ SRS ] AL137141 [ ENTREZ ]

Genbank L05492 [ SRS ] L05492 [ ENTREZ ]

Genbank S54531 [ SRS ] S54531 [ ENTREZ ]

Genbank BC007673 [ SRS ] BC007673 [ ENTREZ ]

Genbank BC010271 [ SRS ] BC010271 [ ENTREZ ]

RefSeq NM_002298 [ SRS ] NM_002298 [ ENTREZ ]

RefSeq NT_086801 [ SRS ] NT_086801 [ ENTREZ ] AceView LCP1 AceView - NCBI TRASER LCP1 Traser - Stanford

Unigene Hs.381099 [ SRS ] Hs.381099 [ NCBI ] HS381099 [ spliceNest ] Protein : pattern, domain, 3D structure

SwissProt P13796 [ SRS] P13796 [ EXPASY ] P13796 [ INTERPRO ]

Prosite PS00019 ACTININ_1 [ SRS ] PS00019 ACTININ_1 [ Expasy ]

Prosite PS00020 ACTININ_2 [ SRS ] PS00020 ACTININ_2 [ Expasy ]

Prosite PS50021 CH [ SRS ] PS50021 CH [ Expasy ]

Prosite PS00018 EF_HAND [ SRS ] PS00018 EF_HAND [ Expasy ]

Interpro IPR001589 Actbind_actnin [ SRS ] IPR001589 Actbind_actnin [ EBI ]

Interpro IPR001715 Calponin-like [ SRS ] IPR001715 Calponin-like [ EBI ]

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 127 - Interpro IPR002048 EF-hand [ SRS ] IPR002048 EF-hand [ EBI ]

Interpro IPR010983 EF_Hand_like [ SRS ] IPR010983 EF_Hand_like [ EBI ] CluSTr P13796

Pfam PF00307 CH [ SRS ] PF00307 CH [ Sanger ] pfam00307 [ NCBI-CDD ]

Pfam PF00036 efhand [ SRS ] PF00036 efhand [ Sanger ] pfam00036 [ NCBI-CDD ]

Prodom PD000012 EF-hand[INRA-Toulouse] Prodom P13796 PLSL_HUMAN [ Domain structure ] P13796 PLSL_HUMAN [ sequences sharing at least 1 domain ] Blocks P13796 Polymorphism : SNP, mutations, diseases OMIM 153430 [ map ] GENECLINICS 153430

SNP LCP1 [dbSNP-NCBI]

SNP NM_002298 [SNP-NCI]

SNP LCP1 [GeneSNPs - Utah] LCP1 [SNP - CSHL] LCP1] [HGBASE - SRS] General knowledge Family LCP1 [UCSC Family Browser] Browser SOURCE NM_002298 SMD Hs.381099 SAGE Hs.381099 Amigo function|actin binding Amigo process|biological_process unknown Amigo function|calcium ion binding Amigo component|cytosol PubGene LCP1 Other databases Probes Probe LCP1 Related clones (RZPD - Berlin) PubMed PubMed 11 Pubmed reference(s) in LocusLink Bibliography Molecular cloning and characterization of plastin, a human leukocyte protein expressed in transformed human fibroblasts. Lin CS, Aebersold RH, Kent SB, Varma M, Leavitt J Mol Cell Biol 1988 Nov;8(11):4659-4668

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 128 - Medline 89096835

Human plastin genes. Comparative gene structure, chromosome location, and differential expression in normal and neoplastic cells. Lin CS, Park T, Chen ZP, Leavitt J J Biol Chem 1993 Feb 5;268(4):2781-2792 Medline 93155095

Activation of the leukocyte plastin gene occurs in most human cancer cells. Park T, Chen ZP, Leavitt J Cancer Res 1994 Apr 1;54(7):1775-1781 Medline 94185016

Interaction of a Dictyostelium member of the plastin/fimbrin family with actin filaments and actin-myosin complexes. Prassler J, Stocker S, Marriott G, Heidecker M, Kellermann J, Gerisch G Mol Biol Cell 1997 Jan;8(1):83-95 Medline 97170068

Cytogenetics in multiple myeloma: a multicenter study of 24 patients with t(11;14)(q13;q32) or its variant. Lai JL, Michaux L, Dastugue N, Vasseur F, Daudignon A, Facon T, Bauters F, Zandecki M Cancer Genet Cytogenet 1998 Jul 15;104(2):133-8 Medline 9666807

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BiblioGene - INIST

Contributor(s) Written 03-1998 Sylvie Galiègue-Zouitina Citation This paper should be referenced as such : Galiègue-Zouitina S . LCP1 (lymphocyte cytosolic protein1). Atlas Genet Cytogenet Oncol Haematol. March 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/LCP1ID95.html

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 129 - © Atlas of Genetics and Cytogenetics in Oncology and Haematology

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 130 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

MTCP1 (Mature T Cell Proliferation 1)

Identity Other C6.1B names Hugo MTCP1 Location Xq28 centromere- Factor VIII - c6.1A - MTCP1 - telomere

MTCP1 (Xq28) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact [email protected]

DNA/RNA

DNA Diagram

Description 7 exons; about 10 kb Transcription complex; alternative splicing: two donor sites in exon 1; transcripts A, the most abondant, ubiquitous: splicing from exon 1 to exon 6; transcripts B, rare: splicing from exon 1 to exon 2; initiation of the transcription: an

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 131 - alternative site of initiation of the transcription in intron 1 has been found in one tumor with a translocation breakpoint in intron 1 Protein

Description p8 MTCP1: coded by transcripts A, 68 amino acids; one domain formed by 3 alpha helices held together by two disulphide bridges in an antiparallel coiled-coil motif p13 MTCP1: coded by transcripts B, 107 amino acides; one domain with a b-barrel topology Expression ubiquitously expressed protein expression undetectable in physiological conditions Localisation mitochondrial cytosol Function unknown unknown Homology none TCL1 (39% identity, similar tridimentional structure) Implicated in Entity t(X;14)(q28;q12) / prolymphocytic leukaemia --> TCRA/D - MTCP1 Disease T-cell prolymphocytic leukaemia Cytogenetics associated with i(8q) Hybrid/Mutated unconstant TCRA-c6.1A transcripts have been described Gene Abnormal none Protein Oncogenesis over expression of p13 MTCP1 is considered as critical in the oncogenetic mechanism

Entity t(X;7)(q28;q35) / prolymphocytic leukaemia --> TCRB - MTCP1 Disease T-cell prolymphocytic leukemia Oncogenesis over expression of p13 MTCP1

External links Nomenclature Hugo MTCP1 GDB MTCP1 Entrez_Gene MTCP1 4515 mature T-cell proliferation 1 Cards Atlas MTCP1ID89 GeneCards MTCP1

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 132 - Ensembl MTCP1 CancerGene MTCP1 Genatlas MTCP1 GeneLynx MTCP1 eGenome MTCP1 euGene 4515 Genomic and cartography MTCP1 - Xq28 chrX:153853606-153863243 - Xq28 (hg17- GoldenPath May_2004) Ensembl MTCP1 - Xq28 [CytoView]

NCBI Genes Cyto Gene Seq [Map View - NCBI] OMIM Disease map [OMIM] HomoloGene MTCP1 Gene and transcription

Genbank Z24459 [ SRS ] Z24459 [ ENTREZ ]

Genbank BC002600 [ SRS ] BC002600 [ ENTREZ ]

Genbank BT006749 [ SRS ] BT006749 [ ENTREZ ]

Genbank X64644 [ SRS ] X64644 [ ENTREZ ]

RefSeq NM_014221 [ SRS ] NM_014221 [ ENTREZ ]

RefSeq NT_086984 [ SRS ] NT_086984 [ ENTREZ ] AceView MTCP1 AceView - NCBI TRASER MTCP1 Traser - Stanford

Unigene Hs.6917 [ SRS ] Hs.6917 [ NCBI ] HS6917 [ spliceNest ] Protein : pattern, domain, 3D structure

SwissProt P56277 [ SRS] P56277 [ EXPASY ] P56277 [ INTERPRO ]

Interpro IPR009069 pMTCP1 [ SRS ] IPR009069 pMTCP1 [ EBI ] CluSTr P56277 Blocks P56277

PDB 1EI0 [ SRS ] 1EI0 [ PdbSum ], 1EI0 [ IMB ]

PDB 1HP8 [ SRS ] 1HP8 [ PdbSum ], 1HP8 [ IMB ]

PDB 2HP8 [ SRS ] 2HP8 [ PdbSum ], 2HP8 [ IMB ] Polymorphism : SNP, mutations, diseases OMIM 300116 [ map ] GENECLINICS 300116

SNP MTCP1 [dbSNP-NCBI]

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 133 - SNP NM_014221 [SNP-NCI]

SNP MTCP1 [GeneSNPs - Utah] MTCP1 [SNP - CSHL] MTCP1] [HGBASE - SRS] General knowledge Family MTCP1 [UCSC Family Browser] Browser SOURCE NM_014221 SMD Hs.6917 SAGE Hs.6917 Amigo process|cell proliferation Amigo component|mitochondrion Amigo process|regulation of cell cycle PubGene MTCP1 Other databases Probes Probe Cancer Cytogenetics (Bari) Probe MTCP1 Related clones (RZPD - Berlin) PubMed PubMed 3 Pubmed reference(s) in LocusLink Bibliography The chromosomal translocation t(X;14)(q28;q11) in T-cell pro-lymphocytic leukaemia breaks within one gene and activates another. Fisch P, Forster A, Sherrington PD, Dyer MJ, Rabbitts TH Oncogene 1993 Dec;8(12):3271-6 Medline 94067776

The MTCP-1/c6.1B gene encodes for a cytoplasmic 8 kD protein overexpressed in T cell leukemia bearing a t(X;14) translocation. Soulier J, Madani A, Cacheux V, Rosenzwajg M, Sigaux F, Stern MH Oncogene 1994 Dec;9(12):3565-70 Medline 95060814

A gene on chromosome Xq28 associated with T-cell prolymphocytic leukemia in two patients with ataxia telangiectasia. Thick J, Mak YF, Metcalfe J, Beatty D, Taylor AM Leukemia 1994 Apr;8(4):564-73 Medline 94202904

Expression of p13MTCP1 is restricted to mature T-cell proliferations with t(X;14) translocations.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 134 - Madani A, Choukroun V, Soulier J, Cacheux V, Claisse JF, Valensi F, Daliphard S, Cazin B, Levy V, Leblond V, Daniel MT, Sigaux F, Stern MH Blood 1996 Mar 1;87(5):1923-7 Medline 96202516

Expression of either the TCL1 oncogene, or transcripts from its homologue MTCP1/c6.1B, in leukaemic and non-leukaemic T cells from ataxia telangiectasia patients. Thick J, Metcalfe JA, Mak YF, Beatty D, Minegishi M, Dyer MJ, Lucas G, Taylor AM Oncogene 1996 Jan 18;12(2):379-86 Medline 96152904

Solution structure of human p8MTCP1, a cysteine-rich protein encoded by the MTCP1 oncogene, reveals a new alpha-helical assembly motif. Barthe P, Yang YS, Chiche L, Hoh F, Strub MP, Guignard L, Soulier J, Stern MH, van Tilbeurgh H, Lhoste JM, Roumestand C J Mol Biol 1997 Dec 19;274(5):801-15 Medline 98070616

Alternative origin of p13MTCP1-encoding transcripts in mature T-cell proliferations with t(X;14) translocations. Gritti C, Choukroun V, Soulier J, Madani A, Dastot H, Leblond V, Radford-Weiss I, Valensi F, Varet B, Sigaux F, Stern MH Oncogene 1997 Sep;15(11):1329-35 Medline 97460719

Solution structure of the recombinant human oncoprotein p13MTCP1. Yang YS, Guignard L, Padilla A, Hoh F, Strub MP, Stern MH, Lhoste JM, Roumestand C J Biomol NMR 1998 Apr;11(3):337-54 Medline 98356286

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BiblioGene - INIST

Contributor(s) Written 03-1998 Marc-Henri Stern Citation This paper should be referenced as such :

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 135 - Stern MH . MTCP1 (Mature T Cell Proliferation 1). Atlas Genet Cytogenet Oncol Haematol. March 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/MTCP1ID89.html

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 136 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

NF2 (neurofibromatosis type 2) (updated: old version not available)

Identity Other SCH names Hugo NF2 Location 22q12.1-12.2 22q12.1-12.2 junction, incidentally not far from EWS DNA/RNA Description exons 17 exons (1-15, 17 constitutive, 16 alternatively spliced); spans 120 kb; open reading frame: 1.8 kb Transcription alternate splicing, in particular after exon 15 Protein

Description called merlin, schwannomin, or SCH; isoform 1 595 amino acids, isoform 2 590 amino acids (due to inclusion of exon 16 in transcript) ; 66 KDa; NH2 - - FERM domain -- large a helix domain -- COOH Expression wide: in lung, kidney, ovary, breast, placenta, neuroblasts; high in fetal brain Localisation membrane associated interacts with integral membrane proteins and actin- cytoskeleton Function membrane-cytoskeleton anchor (as APC also appears to be); role in the development of extraembryonic structures before gastrulation; has characteristics of a tumour suppressor, as has been found in sporadic as well as neurofibromatosis type 2 induced schwannomas and meningiomas Homology ezrin, radixin, moesin, members of the erythrocytes band 4.1 family, especially in the N-terminal FERM domain Mutations Germinal inborn condition of neurofibromatosis type 2 patients: protein truncations due to various frameshift deletions or insertions or nonsense mutations; splice-site or missense mutations are also found; phenotype-genotype correlations are observed (i.e. that severe phenotype are found in cases with protein truncations rather than those with amino acid substitution) Somatic mutation and allele loss events in tumours in neurofibromatosis type 2 and

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 137 - in sporadic schwannomas and meningiomas are in accordance with the two-hit model for neoplasia, as is found in retinoblastoma Implicated in Entity neurofibromatosis type 2 Disease autosomal dominant tumor prone disease; neurofibromatosis type 2 (NF2: the same symbol is used for the disease neurofibromatosis type 2 and the gene) is an hamartoneoplastic syndrome Prognosis hamartomas have a potential towards neoplasia; those, in NF2, are The tumors of NF2 are slow-growing benign schwannomas which do not progress to malignancy and meningiomas

Entity sporadic meningioma

Entity sporadic schwannoma

Entity other tumours: ependymoma; mesothelioma

External links Nomenclature Hugo NF2 GDB NF2 Entrez_Gene NF2 4771 neurofibromin 2 (bilateral acoustic neuroma) Cards Atlas NF2117 GeneCards NF2 Ensembl NF2 CancerGene NF2 Genatlas NF2 GeneLynx NF2 eGenome NF2 euGene 4771 Genomic and cartography GoldenPath NF2 - chr22:28324119-28419137 + 22q12.2 (hg17-May_2004) Ensembl NF2 - 22q12.2 [CytoView]

NCBI Genes Cyto Gene Seq [Map View - NCBI] OMIM Disease map [OMIM]

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 138 - HomoloGene NF2 Gene and transcription

Genbank AF165426 [ SRS ] AF165426 [ ENTREZ ]

Genbank X72655 [ SRS ] X72655 [ ENTREZ ]

Genbank X72670 [ SRS ] X72670 [ ENTREZ ]

Genbank AF113694 [ SRS ] AF113694 [ ENTREZ ]

Genbank AF122827 [ SRS ] AF122827 [ ENTREZ ]

RefSeq NM_000268 [ SRS ] NM_000268 [ ENTREZ ]

RefSeq NM_016418 [ SRS ] NM_016418 [ ENTREZ ]

RefSeq NM_181825 [ SRS ] NM_181825 [ ENTREZ ]

RefSeq NM_181826 [ SRS ] NM_181826 [ ENTREZ ]

RefSeq NM_181827 [ SRS ] NM_181827 [ ENTREZ ]

RefSeq NM_181828 [ SRS ] NM_181828 [ ENTREZ ]

RefSeq NM_181829 [ SRS ] NM_181829 [ ENTREZ ]

RefSeq NM_181830 [ SRS ] NM_181830 [ ENTREZ ]

RefSeq NM_181831 [ SRS ] NM_181831 [ ENTREZ ]

RefSeq NM_181832 [ SRS ] NM_181832 [ ENTREZ ]

RefSeq NM_181833 [ SRS ] NM_181833 [ ENTREZ ]

RefSeq NM_181834 [ SRS ] NM_181834 [ ENTREZ ]

RefSeq NM_181835 [ SRS ] NM_181835 [ ENTREZ ]

RefSeq NT_086921 [ SRS ] NT_086921 [ ENTREZ ] AceView NF2 AceView - NCBI TRASER NF2 Traser - Stanford

Unigene Hs.187898 [ SRS ] Hs.187898 [ NCBI ] HS187898 [ spliceNest ] Protein : pattern, domain, 3D structure

SwissProt P35240 [ SRS] P35240 [ EXPASY ] P35240 [ INTERPRO ] CluSTr P35240 Blocks P35240 Polymorphism : SNP, mutations, diseases OMIM 607379 [ map ] GENECLINICS 607379

SNP NF2 [dbSNP-NCBI]

SNP NM_000268 [SNP-NCI]

SNP NM_016418 [SNP-NCI]

SNP NM_181825 [SNP-NCI]

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 139 - SNP NM_181826 [SNP-NCI]

SNP NM_181827 [SNP-NCI]

SNP NM_181828 [SNP-NCI]

SNP NM_181829 [SNP-NCI]

SNP NM_181830 [SNP-NCI]

SNP NM_181831 [SNP-NCI]

SNP NM_181832 [SNP-NCI]

SNP NM_181833 [SNP-NCI]

SNP NM_181834 [SNP-NCI]

SNP NM_181835 [SNP-NCI]

SNP NF2 [GeneSNPs - Utah] NF2 [SNP - CSHL] NF2] [HGBASE - SRS] General knowledge Family NF2 [UCSC Family Browser] Browser SOURCE NM_000268 SOURCE NM_016418 SOURCE NM_181825 SOURCE NM_181826 SOURCE NM_181827 SOURCE NM_181828 SOURCE NM_181829 SOURCE NM_181830 SOURCE NM_181831 SOURCE NM_181832 SOURCE NM_181833 SOURCE NM_181834 SOURCE NM_181835 SMD Hs.187898 SAGE Hs.187898 Amigo component|cytoplasm Amigo function|cytoskeletal protein binding Amigo component|cytoskeleton Amigo component|cytoskeleton Amigo process|negative regulation of cell cycle Amigo process|negative regulation of cell proliferation

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 140 - Amigo process|perception of sound Amigo component|plasma membrane Amigo function|structural molecule activity PubGene NF2 Other databases Probes Probe NF2 Related clones (RZPD - Berlin) PubMed PubMed 34 Pubmed reference(s) in LocusLink Bibliography A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM, Eldridge R, Kley N, Menon AG, Pulaski K, et al Cell 1993 Mar 12;72(5):791-800 Medline 8453669

Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Rouleau GA, Merel P, Lutchman M, Sanson M, Zucman J, Marineau C, Hoang-Xuan K, Demczuk S, Desmaze C, Plougastel B, et al Nature 1993 Jun 10;363(6429):515-21 Medline 93281181

Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity. Parry DM, Eldridge R, Kaiser-Kupfer MI, Bouzas EA, Pikus A, Patronas N Am J Med Genet 1994 Oct 1;52(4):450-61 Medline 95266606

Germ-line mutations in the neurofibromatosis 2 gene: correlations with disease severity and retinal abnormalities. Parry DM, MacCollin MM, Kaiser-Kupfer MI, Pulaski K, Nicholson HS, Bolesta M, Eldridge R, Gusella JF Am J Hum Genet 1996 Sep;59(3):529-39 Medline 96354546

Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease. Ruttledge MH, Andermann AA, Phelan CM, Claudio JO, Han FY, Chretien N, Rangaratnam S, MacCollin M, Short P, Parry D, Michels V, Riccardi VM, Weksberg R,

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 141 - Kitamura K, Bradburn JM, Hall BD, Propping P, Rouleau GA Am J Hum Genet 1996 Aug;59(2):331-42 Medline 96335702

The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation. McClatchey AI, Saotome I, Ramesh V, Gusella JF, Jacks T Genes Dev 1997 May 15;11(10):1253-65 Medline 97315196

Impaired interaction of naturally occurring mutant NF2 protein with actin-based cytoskeleton and membrane. Deguen B, Merel P, Goutebroze L, Giovannini M, Reggio H, Arpin M, Thomas G Hum Mol Genet 1998 Feb;7(2):217-26 Medline 98087573

Merlin: the neurofibromatosis 2 tumor suppressor.(REVIEW) Gusella JF, Ramesh V, MacCollin M, Jacoby LB Biochim Biophys Acta 1999 Mar 25;1423(2):M29-36 Medline 10214350

Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2. Giovannini M, Robanus-Maandag E, van der Valk M, Niwa-Kawakita M, Abramowski V, Goutebroze L, Woodruff JM, Berns A, Thomas G. Genes Dev 2000 Jul 1;14(13):1617-30 Medline 10887156

The parental origin of new mutations in neurofibromatosis 2 Kluwe L, Mautner V, Parry DM, Jacoby LB, Baser M, Gusella J, Davis K, Stavrou D, MacCollin M Neurogenetics 2000 Sep;3(1):17-24 Medline 11085592

Advances in Neurofibromatosis 2 (NF2): A Workshop Report .(REVIEW) Lim DJ, Rubenstein AE, Evans DG, Jacks T, Seizinger BG, Baser ME, Beebe D, Brackmann DE, Chiocca EA, Fehon RG, Giovannini M, Glazer R, Gusella JF, Gutmann DH, Korf B, Lieberman F, Martuza R, McClatchey AI, Parry DM, Pulst SM, Ramesh V, Ramsey WJ, Ratner N, Rutkowski JL, Ruttledge M, Weinstein DE. J Neurogenet. 2000 Jun;14(2):63-106. Medline 10992163

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Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 142 - Last year automatic search in PubMed publications

BiblioGene - INIST

Contributor(s) Written 09-1997 Jean-Loup Huret Updated 03-1998 Jean-Loup Huret Updated 02-2001 James F Gusella Citation This paper should be referenced as such : Huret JL . NF2 (neurofibromatosis type 2). Atlas Genet Cytogenet Oncol Haematol. September 1997 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/NF2117.html Huret JL . NF2 (neurofibromatosis type 2). Atlas Genet Cytogenet Oncol Haematol. March 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/NF2117.html Gusella JF . NF2 (neurofibromatosis type 2). Atlas Genet Cytogenet Oncol Haematol. February 2001 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/NF2117.html © Atlas of Genetics and Cytogenetics in Oncology and Haematology

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 143 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

MYCN (myc myelocytomatosis viral related oncogene, neuroblastoma derived)

Identity Hugo MYCN Location 2p24.1 centromeric to DDX1

MYCN (2p24) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact [email protected]

DNA/RNA Description 3 exons Protein

Description 464 amino acids; contains a phosphorylation site, an acidic domain, an HLH motif, and a leucine zipper in C-term; forms heterodimers with MAX and recognize the core concensus sequence CACCTG Expression during fetal development Localisation nuclear

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 144 - Function probable transcription factor; possible role during tissue differentiation Homology with members of the myc family of helix-loop-helix transcription factors Mutations Somatic amplification, either in extrachromosomal double minutes or in homogeneously staining regions within chromosomes (there is amplification when, for exemple, 10 to 1000 copies of a gene are present in a cell); found amplified in a variety of human tumors, in particular in and also in retinoblastoma, small cell lung carcinoma, astrocytoma; level of amplification related to the tumor progression; transgenic mice that overexpress MYCN in neuroectodermal cells develop neuroblastoma Implicated in Entity neuroblastoma Oncogenesis MYCN amplification is found in 15% of neuroblastoma, is an adverse prognostic feature per se, and is often associated with other adverse features (older age, abdominal tumor, advanced disease, and high lactate dehydrogenase, ferritin, and neuron-specific enolase serum levels)

External links Nomenclature Hugo MYCN GDB MYCN MYCN 4613 v-myc myelocytomatosis viral related oncogene, Entrez_Gene neuroblastoma derived (avian) Cards Atlas NMYC112 GeneCards MYCN Ensembl MYCN CancerGene MYCN Genatlas MYCN GeneLynx MYCN eGenome MYCN euGene 4613 Genomic and cartography MYCN - 2p24.1 chr2:16032644-16037721 + 2p24.3 (hg17- GoldenPath May_2004) Ensembl MYCN - 2p24.3 [CytoView]

NCBI Genes Cyto Gene Seq [Map View - NCBI]

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 145 - OMIM Disease map [OMIM] HomoloGene MYCN Gene and transcription

Genbank AJ242956 [ SRS ] AJ242956 [ ENTREZ ]

Genbank M13228 [ SRS ] M13228 [ ENTREZ ]

Genbank M13241 [ SRS ] M13241 [ ENTREZ ]

Genbank M18090 [ SRS ] M18090 [ ENTREZ ]

Genbank X02363 [ SRS ] X02363 [ ENTREZ ]

RefSeq NM_005378 [ SRS ] NM_005378 [ ENTREZ ]

RefSeq NT_086610 [ SRS ] NT_086610 [ ENTREZ ] AceView MYCN AceView - NCBI TRASER MYCN Traser - Stanford

Unigene Hs.25960 [ SRS ] Hs.25960 [ NCBI ] HS25960 [ spliceNest ] Protein : pattern, domain, 3D structure

SwissProt P04198 [ SRS] P04198 [ EXPASY ] P04198 [ INTERPRO ]

Prosite PS50888 HLH [ SRS ] PS50888 HLH [ Expasy ]

Interpro IPR001092 HLH_basic [ SRS ] IPR001092 HLH_basic [ EBI ]

Interpro IPR002418 TF_Myc [ SRS ] IPR002418 TF_Myc [ EBI ] CluSTr P04198

Pfam PF00010 HLH [ SRS ] PF00010 HLH [ Sanger ] pfam00010 [ NCBI-CDD ]

Pfam PF01056 Myc_N [ SRS ] PF01056 Myc_N [ Sanger ] pfam01056 [ NCBI-CDD ] Blocks P04198 Polymorphism : SNP, mutations, diseases OMIM 164840 [ map ] GENECLINICS 164840

SNP MYCN [dbSNP-NCBI]

SNP NM_005378 [SNP-NCI]

SNP MYCN [GeneSNPs - Utah] MYCN [SNP - CSHL] MYCN] [HGBASE - SRS] General knowledge Family MYCN [UCSC Family Browser] Browser SOURCE NM_005378 SMD Hs.25960 SAGE Hs.25960 Amigo component|chromatin

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 146 - Amigo component|nucleus Amigo function|protein binding Amigo process|regulation of transcription from Pol II promoter Amigo function|transcription factor activity PubGene MYCN Other databases Probes Probe MYC-N (2p24.3) in normal cells (Bari) Probe MYCN Related clones (RZPD - Berlin) PubMed PubMed 35 Pubmed reference(s) in LocusLink Bibliography Transposition and amplification of oncogene-related sequences in human neuroblastomas. Kohl NE, Kanda N, Schreck RR, Bruns G, Latt SA, Gilbert F, Alt FW Cell 1983 Dec;35(2 Pt 1):359-67 Medline 84082061

MYCN oncogene amplification in neuroblastoma is associated with worse prognosis, except in stage 4s: the Italian experience with 295 children. Tonini GP, Boni L, Pession A, Rogers D, Iolascon A, Basso G, Cordero di Montezemolo L, Casale F, Pession A, Perri P, Mazzocco K, Scaruffi P, Lo Cunsolo C, Marchese N, Milanaccio C, Conte M, Bruzzi P, De Bernardi B J Clin Oncol 1997 Jan;15(1):85-93 Medline 97149320

Targeted expression of MYCN causes neuroblastoma in transgenic mice. Weiss WA, Aldape K, Mohapatra G, Feuerstein BG, Bishop JM EMBO J 1997 Jun 2;16(11):2985-95 Medline 97357287

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Contributor(s)

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 147 - Written 03-1998 Jean-Loup Huret Citation This paper should be referenced as such : Huret JL . MYCN (myc myelocytomatosis viral related oncogene, neuroblastoma derived). Atlas Genet Cytogenet Oncol Haematol. March 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/NMYC112.html

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 148 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

POU2AF1 (POU domain, class 2, associating factor 1)

Identity Other OBF1 (Oct binding factor 1) names BOB1 OCA-B Hugo POU2AF1 Location 11q23.1 telomeric to ATM

POU2AF1 (11q23) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact

DNA/RNA

DNA Diagram

Description spans on a 30 kb genomic fragment; five exons; large fifth exon, with many 3' -UTR repetitive elements, two pyrimidine rich regions (a

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 149 - duplicated CT- rich region and a [CCTT]n tetranucleotide tandem repeat) and a 282 nucleotides long Alu element Transcription 3.4 kb mRNA; coding sequence: 770 bp, spanning from the end of exon 1 to the beginning of exon 5

Protein

Description 256 amino acids; 27.4 kDa; proline rich protein with no recognizable domain or motifs Expression constitutively expressed in B-cells and inducible in T-cells Localisation nuclear Function B-cell specific transcriptional coactivator: involved in the transcription of immunoglobulin genes through recruitment to the highly conserved octamer site of immunoglobulin promoters, mediated by either Oct-1 or Oct-2 transcription factor; forms a ternary complex on DNA together with either Oct-1 or Oct-2 transcription factor; is essential for the response of B- cells to antigens and is required for the formation of germinal centres no homology to known proteins.

Implicated in Entity t(3;11)(q27;q23.1)/ NHL --> BCL6 - OBF1 Disease NHL Cytogenetics found in complex caryotypes Hybrid/Mutated 5' BOB1- 3' BCL6 and 5' BCL6 - 3'BOB1, leading to two fusion Gene transcripts Abnormal no fusion protein, but promoter exchange between both partner genes Protein

External links Nomenclature Hugo POU2AF1 GDB POU2AF1 Entrez_Gene POU2AF1 5450 POU domain, class 2, associating factor 1 Cards Atlas OBF94 GeneCards POU2AF1

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 150 - Ensembl POU2AF1 CancerGene POU2AF1 Genatlas POU2AF1 GeneLynx POU2AF1 eGenome POU2AF1 euGene 5450 Genomic and cartography POU2AF1 - 11q23.1 chr11:110728192-110755627 - 11q23.1 GoldenPath (hg17-May_2004) Ensembl POU2AF1 - 11q23.1 [CytoView]

NCBI Genes Cyto Gene Seq [Map View - NCBI] OMIM Disease map [OMIM] HomoloGene POU2AF1 Gene and transcription

Genbank BC032549 [ SRS ] BC032549 [ ENTREZ ]

Genbank X83504 [ SRS ] X83504 [ ENTREZ ]

Genbank Z47550 [ SRS ] Z47550 [ ENTREZ ]

Genbank Z49194 [ SRS ] Z49194 [ ENTREZ ]

RefSeq NM_006235 [ SRS ] NM_006235 [ ENTREZ ]

RefSeq NT_086787 [ SRS ] NT_086787 [ ENTREZ ] AceView POU2AF1 AceView - NCBI TRASER POU2AF1 Traser - Stanford

Unigene Hs.2407 [ SRS ] Hs.2407 [ NCBI ] HS2407 [ spliceNest ] Protein : pattern, domain, 3D structure

SwissProt Q16633 [ SRS] Q16633 [ EXPASY ] Q16633 [ INTERPRO ] CluSTr Q16633 Blocks Q16633 Polymorphism : SNP, mutations, diseases OMIM 601206 [ map ] GENECLINICS 601206

SNP POU2AF1 [dbSNP-NCBI]

SNP NM_006235 [SNP-NCI]

SNP POU2AF1 [GeneSNPs - Utah] POU2AF1 [SNP - CSHL] POU2AF1] [HGBASE - SRS] General knowledge Family POU2AF1 [UCSC Family Browser] Browser

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 151 - SOURCE NM_006235 SMD Hs.2407 SAGE Hs.2407 Amigo process|humoral immune response Amigo component|nucleus Amigo process|regulation of transcription, DNA-dependent Amigo function|transcription coactivator activity Amigo process|transcription from Pol II promoter PubGene POU2AF1 Other databases Probes Probe Cancer Cytogenetics (Bari) Probe POU2AF1 Related clones (RZPD - Berlin) PubMed PubMed 8 Pubmed reference(s) in LocusLink

Bibliography OBF-1, a novel B cell-specific coactivator that stimulates immunoglobulin promoter activity through association with octamer-binding proteins Strubin M, Newell JW, Matthias P Cell 1995 Feb 10;80(3):497-506 Medline 95163103

A B-cell coactivator of octamer-binding transcription factors. Gstaiger M, Knoepfel L, Georgiev O, Schaffner W, Hovens CM Nature 1995 Jan 26;373(6512):360-2 Medline 95132016

Cloning, functional characterization, and mechanism of action of the B-cell- specific transcriptional coactivator OCA-B. Luo Y, Roeder RG Mol Cell Biol 1995 Aug;15(8):4115-24 Medline 95349577

Heterogeneity of breakpoints at the transcriptional co-activator gene, BOB-1, in lymphoproliferative disease. Yuille MA, Galiegue-Zouitina S, Hiorns LR, Jadayel D, De Schouwer PJ, Catovsky D, Dyer MJ, Kerckaert JP Leukemia 1996 Sep;10(9):1492-6

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 152 - Medline 96352676

B-cell-specific coactivator OBF-1/OCA-B/Bob1 required for immune response and germinal centre formation. Schubart DB, Rolink A, Kosco-Vilbois MH, Botteri F, Matthias P Nature 1996 Oct 10;383(6600):538-42 Medline 97002327

Inducible expression and phosphorylation of coactivator BOB.1/OBF.1 in T cells. Zwilling S, Dieckmann A, Pfisterer P, Angel P, Wirth T Science 1997 Jul 11;277(5323):221-5 Medline 97362321

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BiblioGene - INIST

Contributor(s) Written 03-1998 Sylvie Galiègue-Zouitina Citation This paper should be referenced as such : Galiègue-Zouitina S . POU2AF1 (POU domain, class 2, associating factor 1). Atlas Genet Cytogenet Oncol Haematol. March 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/OBF94.html

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 153 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

ABCB1

Identity Other PGY1 (P glycoprotein1/ multidrug resistance 1) names MDR1 (multidrug resistance 1) Hugo ABCB1 Location 7q21.2 DNA/RNA Description spans on a 120 kb genomic fragment; separated from MDR3 gene (which is transcribed in the same direction) by only 34 kb of intergenic DNA Transcription 5 kb mRNA Protein

Description the protein is called P-glycoprotein; 170 kDa transmembrane glycoprotein which includes 10-15 kDa of N-term glycosylation; the N-term half of the molecule contains 6 transmembrane domains, followed by a large cytoplasmic domain with an ATP binding site, and then a second section with 6 transmembrane domains and an ATP binding site which shows over 65% of amino acid similarity with the first half of the polypeptide Expression normally expressed at secretory surface of a number of tissues, including biliary canaliculi, proximal tubules of the kidney, intestinal and colonic epithelium; hematopoietic stem cells express high levels of P-glycoprotein; overexpressed in many multidrug resistant cell lines and in tumor cells resistant to chemotherapy Localisation mainly at the cell membrane, with a secondary localisation at the Golgi apparatus Function the P-glycoprotein is an energy-dependent efflux pump involved in extrusion of many types of lypophilic coumpounds; it may acts in normal tissues as a protective mechanism against noxious xenobiotics and as a transporter of endogenous substrates; in tumour cells, the drug efflux pump results in a decrease in intracellular drug concentration Homology closely related gene to MDR3 (also called PGY3), located at the same chromosomal site but not implicated in multidrug resistance; there are 3 murine homolog genes (mdr1, mdr2, mdr3) out of which only 2 (mdr1 and

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 154 - mdr3) are involved in multidrug resistance; member of a large superfamily of transmembrane transporter proteins named ATP Binding Cassette (ABC) transporters or Traffic ATPases; structural homology with other ABC transporter proteins (CFTR, MRP) Implicated in Entity tumor cells resistance Disease tumor cells resistance to a wide variety of antineoplasic agents: doxorubicin, daunorubicin, vinblastine, vincristine, colchicine, actinomycine D, etoposide, tenoposide, mitoxantrone, homoharringtonine; this phenomenon is named "multidrug resistance" (MDR); P-glycoprotein is the main protein responsible for the MDR phenotype; however, other agents may be involved in MDR, independently or in association with P- glycoprotein: "multidrug resistant associated protein" (MRP), "lung resistance protein" (LRP), "anthracycline associated resistance protein" (ARX)

Entity leukemias Disease In leukemia, MDR1 overexpression is observed in patients with a lower complete remission rate and with a shortening of overall survival; frequently associated with intermediate and poor prognosis karyotype; in ANLL, approximately 50% of patients are MDR positive at diagnosis (range 22-70%) and the MDR phenotype is more frequently observed in CD34+ leukemias; in ALL, the average number of MDR-positive cases is 22% at diagnosis

Entity tumour cell lines: in numerous continuous tumour cell lines which acquired experimentally a MDR phenotype when cultured with progressively increasing drug concentration, the acquisition of MDR was associated with hyperexpression of P-glycoprotein; for the higher levels of expression, southern blots revealed an increase in the number of copies of the MDR1 gene per cell Cytogenetics the genomic amplification of MDR1 appears as extrachromosomic "double-minute chromosomes" (DM) or intrachromosomic "homogeneous staining regions" (HSR) Oncogenesis amplification

External links Nomenclature Hugo ABCB1 GDB ABCB1

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 155 - ABCB1 5243 ATP-binding cassette, sub-family B (MDR/TAP), member Entrez_Gene 1 Cards Atlas PGY1ID105 GeneCards ABCB1 Ensembl ABCB1 CancerGene ABCB1 Genatlas ABCB1 GeneLynx ABCB1 eGenome ABCB1 euGene 5243 Genomic and cartography ABCB1 - 7q21.2 chr7:86777599-86987215 - 7q21.12 (hg17- GoldenPath May_2004) Ensembl ABCB1 - 7q21.12 [CytoView]

NCBI Genes Cyto Gene Seq [Map View - NCBI] OMIM Disease map [OMIM] HomoloGene ABCB1 Gene and transcription

Genbank AF016534 [ SRS ] AF016534 [ ENTREZ ]

Genbank CH236949 [ SRS ] CH236949 [ ENTREZ ]

Genbank M29422 [ SRS ] M29422 [ ENTREZ ]

Genbank M29423 [ SRS ] M29423 [ ENTREZ ]

Genbank M29424 [ SRS ] M29424 [ ENTREZ ]

RefSeq NM_000927 [ SRS ] NM_000927 [ ENTREZ ]

RefSeq NT_086723 [ SRS ] NT_086723 [ ENTREZ ] AceView ABCB1 AceView - NCBI TRASER ABCB1 Traser - Stanford

Unigene Hs.489033 [ SRS ] Hs.489033 [ NCBI ] HS489033 [ spliceNest ] Protein : pattern, domain, 3D structure

SwissProt P08183 [ SRS] P08183 [ EXPASY ] P08183 [ INTERPRO ]

Prosite PS50929 ABC_TM1F [ SRS ] PS50929 ABC_TM1F [ Expasy ]

PS00211 ABC_TRANSPORTER_1 [ SRS ] PS00211 Prosite ABC_TRANSPORTER_1 [ Expasy ]

PS50893 ABC_TRANSPORTER_2 [ SRS ] PS50893 Prosite ABC_TRANSPORTER_2 [ Expasy ]

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 156 - Interpro IPR003593 AAA_ATPase [ SRS ] IPR003593 AAA_ATPase [ EBI ]

Interpro IPR001140 ABC_TM_transpt [ SRS ] IPR001140 ABC_TM_transpt [ EBI ]

Interpro IPR003439 ABC_transporter [ SRS ] IPR003439 ABC_transporter [ EBI ] CluSTr P08183

PF00664 ABC_membrane [ SRS ] PF00664 ABC_membrane [ Sanger Pfam ] pfam00664 [ NCBI-CDD ] Pfam PF00005 ABC_tran [ SRS ] PF00005 ABC_tran [ Sanger ] pfam00005 [ NCBI-CDD ]

Smart SM00382 AAA [EMBL]

Prodom PD000006 ABC_transporter[INRA-Toulouse] Prodom P08183 MDR1_HUMAN [ Domain structure ] P08183 MDR1_HUMAN [ sequences sharing at least 1 domain ] Blocks P08183 Polymorphism : SNP, mutations, diseases OMIM 171050 [ map ] GENECLINICS 171050

SNP ABCB1 [dbSNP-NCBI]

SNP NM_000927 [SNP-NCI]

SNP ABCB1 [GeneSNPs - Utah] ABCB1 [SNP - CSHL] ABCB1] [HGBASE - SRS] General knowledge Family ABCB1 [UCSC Family Browser] Browser SOURCE NM_000927 SMD Hs.489033 SAGE Hs.489033 Amigo function|ATP binding Amigo function|ATPase activity function|ATPase activity, coupled to transmembrane movement of Amigo substances Amigo component|integral to membrane Amigo component|membrane fraction Amigo function|nucleotide binding Amigo process|response to drug Amigo process|transport Amigo function|transporter activity BIOCARTA Multi-Drug Resistance Factors BIOCARTA Nuclear Receptors in Lipid Metabolism and Toxicity

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 157 - BIOCARTA Hypoxia and p53 in the Cardiovascular system PubGene ABCB1 Other databases Probes Probe ABCB1 Related clones (RZPD - Berlin) PubMed PubMed 130 Pubmed reference(s) in LocusLink Bibliography Autonomously replicating episomes contain mdr1 genes in a multidrug-resistant human cell line. Ruiz JC, Choi KH, von Hoff DD, Robinson IB, Wahl GM Mol Cell Biol 1989 Jan;9(1):109-15 Medline 89181559

Multidrug resistance in acute myeloid leukemia. Baer MR, Bloomfield CD J Natl Cancer Inst 1991 May 15;83(10):663-5 Medline 91218182

Double minute chromosomes carrying the human multidrug resistance 1 and 2 genes are generated from the dimerization of submicroscopic circular DNAs in colchicine-selected KB carcinoma cells. Schoenlein PV, Shen DW, Barrett JT, Pastan I, Gottesman MM Mol Biol Cell 1992 May;3(5):507-20 Medline 92305422

Cell biological mechanisms of multidrug resistance in tumors. Simon SM, Schindler M Proc Natl Acad Sci U S A 1994 Apr 26;91(9):3497-504 Medline 94224767

A YAC-based contig of 1.5 Mb spanning the human multidrug resistance gene region and delineating the amplification unit in three human multidrug-resistant cell lines. Torigoe K, Sato S, Kusaba H, Kohno K, Kuwano M, Okumura K, Green ED, Tsui LC, Scherer SW, Schlessinger D, et al Genome Res 1995 Oct;5(3):233-44 Medline 96159529

P-glycoprotein multidrug resistance and cancer. Bosch I, Croop J

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 158 - Biochim Biophys Acta 1996 Oct 9;1288(2):F37-54 Medline 97030691

P-glycoprotein and multidrug resistance. Gottesman MM, Pastan I, Ambudkar SV Curr Opin Genet Dev 1996 Oct;6(5):610-7 Medline 97094618

The MDR phenotype in hematologic malignancies: prognostic relevance and future perspectives. Hegewisch-Becker S, Hossfeld DK Ann Hematol 1996 Mar;72(3):105-17 Medline 96305024

Sequential emergence of MRP- and MDR1-gene over-expression as well as MDR1- gene translocation in homoharringtonine-selected K562 human leukemia cell lines. Zhou DC, Ramond S, Viguie F, Faussat AM, Zittoun R, Marie JP Int J Cancer 1996 Jan 26;65(3):365-71 Medline 96163524

Multidrug resistance gene expression in acute myeloid leukemia: major prognosis significance for in vivo drug resistance to induction treatment. Hunault M, Zhou D, Delmer A, Ramond S, Viguie F, Cadiou M, Perrot JY, Levy V, Rio B, Cymbalista F, Zittoun R, Marie JP Ann Hematol 1997 Feb;74(2):65-71 Medline 97217354

Functional expression of MDR-1 in acute myeloid leukemia: correlation with the clinical-biological, immunophenotypical, and prognostic disease characteristics. Martinez A, San Miguel JF, Valverde B, Barez A, Moro MJ, Garcia-Marcos MA, Perez- Simon JA, Vidriales B, Orfao A Ann Hematol 1997 Sep;75(3):81-6 Medline 98034850

MDR 1 expression is an independent prognostic factor for response and survival in de novo acute myeloid leukaemia. van den Heuvel-Eibrink MM, van der Holt B, te Boekhorst PA, Pieters R, Schoester M, Lowenberg B, Sonneveld P Br J Haematol 1997 Oct;99(1):76-83 Medline 98022464

The prognostic significance of the expression and function of multidrug

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 159 - resistance transporter proteins in acute myeloid leukemia: studies of the Southwest Oncology Group Leukemia Research Program. Willman CL Semin Hematol 1997 Oct;34(4 Suppl 5):25-33 Medline 98073303

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BiblioGene - INIST

Contributor(s) Written 03-1998 Franck Viguié Citation This paper should be referenced as such : Viguié F . ABCB1. Atlas Genet Cytogenet Oncol Haematol. March 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/PGY1ID105.html

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 160 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

TAL1 (T-cell acute leukemia 1)

Identity Other SCL (stem cell leukaemia), TCL5 (T cell leukaemia 5) names Hugo TAL1 Location 1p32

DNA/RNA

DNA diagram

Description 8 exons; 16 kb; SIL (a different gene) sits 90 kb further in 5' Transcription (complex) alternate splicing of: 1A with 2A, or 3 vs 1B, 2B,3 ...or directly 4, 5, 6

Protein

Description 331 amino acids for the major form of 48 KDa; a truncated form of 26 KDa only in some T-ALL; domains: prolin rich in N-trem; poly Gly; basic Helix- Loop-Helix from the exon 6. Expression in hematopoietic stem cells, erythroid and megakaryocytic lineages of the adult and in the embryonic brain; indispensable for the genesis of the hematopoietic system. Function transcription factor; exhibits sequence-specific DNA binding activity when in dimers with another bHLH protein such as E2A (DNA specific sequences are: CANNTG, especially: CAGATG); direct interactions of the bHLH with the LIM domain of RBTN2 or RBTN1. Homology TAL2 in 9q32; LYL1 in 19p13; more distantly: MYC and other members of the MYC family of Helix-Loop-Helix transcription factors.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 161 - Implicated in Entity t(1;7)(p32;q34) or t(1;14)(p32;q11)/T-ALL --> TAL1-TCRB or TAL1- TCRD Disease T-cell ALL Prognosis is not too poor, compared to other T-ALL

Entity T-ALL with normal karyotype, but with submicroscopic deletions of part of TAL1 in the 5' region --> SIL-TAL1. Disease found in 10 to 30 % of T-ALL with a normal karyotype Hybrid/Mutated deletions which place SIL (SCL interrupting sequence) in close 5' of Gene TAL1; hybrid gene with exon 1 from SIL. Abnormal TAL1 is under the promoter sequences controle of SIL, a gene active Protein during T cell development.

Entity t(1;3)(p32;p21)/T-ALL --> TAL1-TCTA Disease T-cell ALL

Breakpoints

Note mainly in 5' in a 1 kb region; but also dispersed in rare cases

External links Nomenclature Hugo TAL1 GDB TAL1 Entrez_Gene TAL1 6886 T-cell acute lymphocytic leukemia 1

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 162 - Cards Atlas TAL1 GeneCards TAL1 Ensembl TAL1 CancerGene TAL1 Genatlas TAL1 GeneLynx TAL1 eGenome TAL1 euGene 6886 Genomic and cartography GoldenPath TAL1 - 1p32 chr1:47393984-47407463 - 1p33 (hg17-May_2004) Ensembl TAL1 - 1p33 [CytoView]

NCBI Genes Cyto Gene Seq [Map View - NCBI] OMIM Disease map [OMIM] HomoloGene TAL1 Gene and transcription

Genbank AJ131016 [ SRS ] AJ131016 [ ENTREZ ]

Genbank AL135960 [ SRS ] AL135960 [ ENTREZ ]

Genbank M63589 [ SRS ] M63589 [ ENTREZ ]

Genbank X58621 [ SRS ] X58621 [ ENTREZ ]

Genbank X58622 [ SRS ] X58622 [ ENTREZ ]

RefSeq NM_003189 [ SRS ] NM_003189 [ ENTREZ ]

RefSeq NT_086582 [ SRS ] NT_086582 [ ENTREZ ] AceView TAL1 AceView - NCBI TRASER TAL1 Traser - Stanford

Unigene Hs.73828 [ SRS ] Hs.73828 [ NCBI ] HS73828 [ spliceNest ] Protein : pattern, domain, 3D structure

SwissProt P17542 [ SRS] P17542 [ EXPASY ] P17542 [ INTERPRO ]

Prosite PS50888 HLH [ SRS ] PS50888 HLH [ Expasy ]

Interpro IPR001092 HLH_basic [ SRS ] IPR001092 HLH_basic [ EBI ] CluSTr P17542

Pfam PF00010 HLH [ SRS ] PF00010 HLH [ Sanger ] pfam00010 [ NCBI-CDD ] Blocks P17542 Polymorphism : SNP, mutations, diseases OMIM 187040 [ map ]

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 163 - GENECLINICS 187040

SNP TAL1 [dbSNP-NCBI]

SNP NM_003189 [SNP-NCI]

SNP TAL1 [GeneSNPs - Utah] TAL1 [SNP - CSHL] TAL1] [HGBASE - SRS] General knowledge Family TAL1 [UCSC Family Browser] Browser SOURCE NM_003189 SMD Hs.73828 SAGE Hs.73828 Amigo function|DNA binding Amigo process|cell differentiation Amigo process|cell proliferation Amigo process|regulation of transcription, DNA-dependent PubGene TAL1 Other databases Probes Probe TAL1 Related clones (RZPD - Berlin) PubMed PubMed 15 Pubmed reference(s) in LocusLink

Bibliography Transcriptional activity of TAL1 in T cell acute lymphoblastic leukemia (T-ALL) requires RBTN1 or -2 and induces TALLA1, a highly specific tumor marker of T- ALL. Ono Y, Fukuhara N, Yoshie O J Biol Chem 1997 Feb 14;272(7):4576-81 Medline 97172541

The TAL1/Scl basic helix-loop-helix protein blocks myogenic differentiation and E- box dependent transactivation. Hofmann TJ, Cole MD Oncogene 1996 Aug 1;13(3):617-24 Medline 96330341

The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages. Porcher C, Swat W, Rockwell K, Fujiwara Y, Alt FW, Orkin SH

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 164 - Cell 1996 Jul 12;86(1):47-57 Medline 96291398

Association of erythroid transcription factors: complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1. Osada H, Grutz G, Axelson H, Forster A, Rabbitts TH Proc Natl Acad Sci U S A 1995 Oct 10;92(21):9585-9 Medline 96003823

Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. Wadman I, Li J, Bash RO, Forster A, Osada H, Rabbitts TH, Baer R EMBO J 1994 Oct 17;13(20):4831-9 Medline 95045374

Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study. Bash RO, Crist WM, Shuster JJ, Link MP, Amylon M, Pullen J, Carroll AJ, Buchanan GR, Smith RG, Baer R Blood 1993 Apr 15;81(8):2110-7 Medline 93229751

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BiblioGene - INIST

Contributor(s) Written 08-1997 Jean-Loup Huret and Marie Claude Labastie Updated 03-1998 Jean-Loup Huret and Marie Claude Labastie Citation This paper should be referenced as such : Huret JL and Labastie MC . TAL1 (T-cell acute leukemia 1). Atlas Genet Cytogenet Oncol Haematol. August 1997 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/TAL1.html

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 165 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

TCL1A (T-cell leukemia/lymphoma 1A)

Identity Other TCL1 (T Cell Leukemia/Lymphoma 1) names Hugo TCL1A Location 14q32.1 DNA/RNA Description 4 exons; telomere - exon 1 to 4 - centromere orientation Transcription 1.3 kb transcripts Protein

Description 114 amino acids; one domain with a b-barrel topology Expression immature T and B lymphoid cells Localisation cytoplasm Function unknown Homology MTCP1 (38 % identity, similar tridimentional structure) Implicated in Entity t(14;14)(q12;q32.1) or inv(14)(q12q32.1) /T-cell malignancies --> TCRA/D - TCL1 Disease mainly T-cell prolymphocytic leukemia (T-PLL); T- cell NHL; T-cell ALL Cytogenetics associated with i(8q) in T-PLL Hybrid/Mutated none Gene Abnormal none Protein Oncogenesis over expression of TCL1 is considered as critical in the oncogenetic mechanism

Entity t(7;14)(q35;q32.1)/T-cell malignancies --> TCRB - TCL1 Disease mainly T-cell prolymphocytic leukemia

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 166 - Cytogenetics associated with i(8q) Hybrid/Mutated none Gene Abnormal none Protein Oncogenesis over expression of TCL1

External links Nomenclature Hugo TCL1A GDB TCL1A Entrez_Gene TCL1A 8115 T-cell leukemia/lymphoma 1A Cards Atlas TCL1ID66 GeneCards TCL1A Ensembl TCL1A CancerGene TCL1 Genatlas TCL1A GeneLynx TCL1A eGenome TCL1A euGene 8115 Genomic and cartography TCL1A - 14q32.1 chr14:95246058-95250201 - 14q32.13 (hg17- GoldenPath May_2004) Ensembl TCL1A - 14q32.13 [CytoView]

NCBI Genes Cyto Gene Seq [Map View - NCBI] OMIM Disease map [OMIM] HomoloGene TCL1A Gene and transcription

Genbank X82241 [ SRS ] X82241 [ ENTREZ ]

Genbank BC003574 [ SRS ] BC003574 [ ENTREZ ]

Genbank BC005831 [ SRS ] BC005831 [ ENTREZ ]

Genbank BC009502 [ SRS ] BC009502 [ ENTREZ ]

Genbank BC009891 [ SRS ] BC009891 [ ENTREZ ]

RefSeq NM_021966 [ SRS ] NM_021966 [ ENTREZ ]

RefSeq NT_086807 [ SRS ] NT_086807 [ ENTREZ ]

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 167 - AceView TCL1A AceView - NCBI TRASER TCL1A Traser - Stanford

Unigene Hs.2484 [ SRS ] Hs.2484 [ NCBI ] HS2484 [ spliceNest ] Protein : pattern, domain, 3D structure

SwissProt P56279 [ SRS] P56279 [ EXPASY ] P56279 [ INTERPRO ]

Interpro IPR004832 TCL1_MTCP1 [ SRS ] IPR004832 TCL1_MTCP1 [ EBI ] CluSTr P56279

PF01840 TCL1_MTCP1 [ SRS ] PF01840 TCL1_MTCP1 [ Sanger Pfam ] pfam01840 [ NCBI-CDD ]

Prodom PD015575 TCL1_MTCP1[INRA-Toulouse] Prodom P56279 TCLA_HUMAN [ Domain structure ] P56279 TCLA_HUMAN [ sequences sharing at least 1 domain ] Blocks P56279

PDB 1JSG [ SRS ] 1JSG [ PdbSum ], 1JSG [ IMB ] Polymorphism : SNP, mutations, diseases OMIM 186960 [ map ] GENECLINICS 186960

SNP TCL1A [dbSNP-NCBI]

SNP NM_021966 [SNP-NCI]

SNP TCL1A [GeneSNPs - Utah] TCL1A [SNP - CSHL] TCL1A] [HGBASE - SRS] General knowledge Family TCL1A [UCSC Family Browser] Browser SOURCE NM_021966 SMD Hs.2484 SAGE Hs.2484 Amigo process|development Amigo component|microsome PubGene TCL1A Other databases Probes Probe TCL1A Related clones (RZPD - Berlin) PubMed PubMed 10 Pubmed reference(s) in LocusLink Bibliography Chromosome walking on the TCL1 locus involved in T-cell neoplasia.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 168 - Virgilio L, Isobe M, Narducci MG, Carotenuto P, Camerini B, Kurosawa N, Abbas-ar- Rushdi, Croce CM, Russo G Proc Natl Acad Sci U S A 1993 Oct 15;90(20):9275-9 Medline 94022358

Characterization and localization of the TCL-1 oncogene product. Fu TB, Virgilio L, Narducci MG, Facchiano A, Russo G, Croce CM Cancer Res 1994 Dec 15;54(24):6297-301 Medline 95079394

Identification of the TCL1 gene involved in T-cell malignancies Virgilio L, Narducci MG, Isobe M, Billips LG, Cooper MD, Croce CM, Russo G Proc Natl Acad Sci U S A 1994 Dec 20;91(26):12530-4 Medline 95107991

TCL1 oncogene activation in preleukemic T cells from a case of ataxia- telangiectasia. Narducci MG, Virgilio L, Isobe M, Stoppacciaro A, Elli R, Fiorilli M, Carbonari M, Antonelli A, Chessa L, Croce CM, et al Blood 1995 Sep 15;86(6):2358-64 Medline 95391995

TCL1 is overexpressed in patients affected by adult T-cell leukemias. Narducci MG, Stoppacciaro A, Imada K, Uchiyama T, Virgilio L, Lazzeri C, Croce CM, Russo G Cancer Res 1997 Dec 15;57(24):5452-6 Medline 98069837

The murine Tcl1 oncogene: embryonic and lymphoid cell expression. Narducci MG, Virgilio L, Engiles JB, Buchberg AM, Billips L, Facchiano A, Croce CM, Russo G, Rothstein JL Oncogene 1997 Aug 18;15(8):919-26 Medline 97430049

Crystal structure of p14TCL1, an oncogene product involved in T-cell prolymphocytic leukemia, reveals a novel beta-barrel topology.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 169 - Hoh F, Yang YS, Guignard L, Padilla A, Stern MH, Lhoste JM, van Tilbeurgh H Structure 1998 Feb 15;6(2):147-55 Medline 98179932 REVIEW articles automatic search in PubMed Last year automatic search in PubMed publications

BiblioGene - INIST

Contributor(s) Written 03-1998 Marc-Henri Stern Citation This paper should be referenced as such : Stern MH . TCL1A (T-cell leukemia/lymphoma 1A). Atlas Genet Cytogenet Oncol Haematol. March 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/TCL1ID66.html © Atlas of Genetics and Cytogenetics in Oncology and Haematology

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 170 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

TCTA (T-cell leukemia translocation-associated gene)

Identity Hugo TCTA Location 3p21 DNA/RNA

DNA diagram

Transcription 2.1 kb mRNA Protein

Description 103 amino acids; 11 kDa; rich in hydrophobic amino acids (residues 41-61) Expression wide, especially in kidneys Localisation may be a membrane associated protein, as there is a hydrophobic domain Function unknown Homology none is known Implicated in Entity t(1;3)(p32;p21)/T-cell ALL --> TAL1 - TCTA Disease T-cell ALL Hybrid/Mutated head to head orientation of TAL1 and TCTA Gene Abnormal no fusion protein, but possibly promoter exchange and gene Protein disregulation

To be noted

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 171 - on day 04 Feb 1998, nothing new has appeared since the above coted paper External links Nomenclature Hugo TCTA GDB TCTA Entrez_Gene TCTA 6988 T-cell leukemia translocation altered gene Cards Atlas TCTA GeneCards TCTA Ensembl TCTA CancerGene TCTA Genatlas TCTA GeneLynx TCTA eGenome TCTA euGene 6988 Genomic and cartography TCTA - 3p21 chr3:49424643-49428912 + 3p21.31 (hg17- GoldenPath May_2004) Ensembl TCTA - 3p21.31 [CytoView]

NCBI Genes Cyto Gene Seq [Map View - NCBI] OMIM Disease map [OMIM] HomoloGene TCTA Gene and transcription

Genbank AK000824 [ SRS ] AK000824 [ ENTREZ ]

Genbank BC005157 [ SRS ] BC005157 [ ENTREZ ]

Genbank CR457411 [ SRS ] CR457411 [ ENTREZ ]

Genbank L41143 [ SRS ] L41143 [ ENTREZ ]

RefSeq NM_022171 [ SRS ] NM_022171 [ ENTREZ ]

RefSeq NT_086638 [ SRS ] NT_086638 [ ENTREZ ] AceView TCTA AceView - NCBI TRASER TCTA Traser - Stanford

Unigene Hs.517962 [ SRS ] Hs.517962 [ NCBI ] HS517962 [ spliceNest ] Protein : pattern, domain, 3D structure

SwissProt P57738 [ SRS] P57738 [ EXPASY ] P57738 [ INTERPRO ]

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 172 - CluSTr P57738 Blocks P57738 Polymorphism : SNP, mutations, diseases OMIM 600690 [ map ] GENECLINICS 600690

SNP TCTA [dbSNP-NCBI]

SNP NM_022171 [SNP-NCI]

SNP TCTA [GeneSNPs - Utah] TCTA [SNP - CSHL] TCTA] [HGBASE - SRS] General knowledge Family TCTA [UCSC Family Browser] Browser SOURCE NM_022171 SMD Hs.517962 SAGE Hs.517962 PubGene TCTA Other databases Probes Probe TCTA Related clones (RZPD - Berlin)

PubMed PubMed 2 Pubmed reference(s) in LocusLink Bibliography Cloning and characterization of TCTA, a gene located at the site of a t(1;3) translocation. Aplan PD, Johnson BE, Russell E, Chervinsky DS, Kirsch IR Cancer Res 1995 May 1;55(9):1917-21 Medline 95246031

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BiblioGene - INIST

Contributor(s) Written 01-1998 Jean-Loup Huret Updated 03-1998 Jean-Loup Huret

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 173 - Citation This paper should be referenced as such : Huret JL . TCTA (T-cell leukemia translocation-associated gene). Atlas Genet Cytogenet Oncol Haematol. January 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/TCTA.html Huret JL . TCTA (T-cell leukemia translocation-associated gene). Atlas Genet Cytogenet Oncol Haematol. March 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/TCTA.html

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 174 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

FIM (fused in myeloproliferative disorders) (updated: old version not available)

Identity Other ZNF198 (zinc finger protein 198). names RAMP Hugo FIM Location 13q12 proximal from FLT1 and FLT3

FIM (13q12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact [email protected]

DNA/RNA Description full length cDNA: 5,016 bp; a single open reading frame of 4,137 bp; alternative spliced cDNA variant Transcription main transcripts: 5.0 and 7.5 kb

Protein

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 175 -

Description 1 379 amino acids; hydrophobic protein containing several motifs: a N- terminal cystein-rich region containing ten repeats with the consensus sequence C-X2-C-X18-24-F/Y-C-X3-C, which correspond to a novel zinc finger motifs, a highly hydrophobic proline-rich stretch, and a bipartite nuclear localization signal Expression wide Localisation cell nucleus and nucleolus; within the nucleolus, colocalizes with UBF (Upstream Binding Factor) Function may be involved in the regulation of rRNA transcription Homology FIM is related to DXS6673E, a gene which may be related with mental retardation

Implicated in Entity t(8;13)(p12;q12)/ANLL-NHL --> 5' FIM - 3' FGFR1 ; stem-cell myeloproliferative disorder associated with the 8p12 chromosomal translocations; fused to the catalytic domain of FGFR1 Disease stem-cell myeloproliferative disorder characterized by myeloid hyperplasia, T -cell lymphoblastic leukemia/lymphoma and peripheral blood eosinophilia, and it generally progresses to acute myeloid leukemia; specific to the 8p12 chromosomal region Prognosis very poor (median survival: 12 mths) Cytogenetics usually, t(8;13)(p12;q12) occurs as a single anomaly; duplication of the der(13) was found during disease progression, suggesting that the crucial event might lie on this derivative chromosome; additional abnormalities:+8, +21

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Hybrid/Mutated 5' FIM - 3' FGFR1; localisation: der(13) Gene Abnormal aberrant tyrosine kinase composed of the N-term two-thirds of FIM Protein (retaining the 10 putative zinc finger motifs), and the FGFR1 intracellular region minus the major part of the juxtamembrane domain Oncogenesis constitutive kinase activity of FGFR1 through constitutive activation of FGFR1 signal transduction pathways via constitutive dimerization capability mediated by the FIM N-term zinc finger sequences

External links Nomenclature Hugo FIM GDB ZNF198 Entrez_Gene ZNF198 7750 zinc finger protein 198 Cards Atlas ZNF198ID114 GeneCards ZNF198 Ensembl ZNF198 CancerGene ZNF198 Genatlas ZNF198 GeneLynx ZNF198 eGenome ZNF198 euGene 7750

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 177 - Genomic and cartography ZNF198 - 13q12 chr13:19430810-19558939 + 13q12.11 (hg17- GoldenPath May_2004) Ensembl ZNF198 - 13q12.11 [CytoView]

NCBI Genes Cyto Gene Seq [Map View - NCBI] OMIM Disease map [OMIM] HomoloGene ZNF198 Gene and transcription

Genbank AJ007676 [ SRS ] AJ007676 [ ENTREZ ]

Genbank AL137119 [ SRS ] AL137119 [ ENTREZ ]

Genbank AL138688 [ SRS ] AL138688 [ ENTREZ ]

Genbank AF012126 [ SRS ] AF012126 [ ENTREZ ]

Genbank AF035374 [ SRS ] AF035374 [ ENTREZ ]

RefSeq NM_003453 [ SRS ] NM_003453 [ ENTREZ ]

RefSeq NM_197968 [ SRS ] NM_197968 [ ENTREZ ]

RefSeq NT_086801 [ SRS ] NT_086801 [ ENTREZ ] AceView ZNF198 AceView - NCBI TRASER ZNF198 Traser - Stanford

Unigene Hs.507433 [ SRS ] Hs.507433 [ NCBI ] HS507433 [ spliceNest ] Protein : pattern, domain, 3D structure

SwissProt Q9UBW7 [ SRS] Q9UBW7 [ EXPASY ] Q9UBW7 [ INTERPRO ]

Interpro IPR011017 TRASH [ SRS ] IPR011017 TRASH [ EBI ]

Interpro IPR010507 ZF-MYM [ SRS ] IPR010507 ZF-MYM [ EBI ] CluSTr Q9UBW7 Pfam PF06467 zf-MYM [ SRS ] PF06467 zf-MYM [ Sanger ] pfam06467 [ NCBI-CDD ]

Smart SM00746 TRASH [EMBL] Blocks Q9UBW7 Polymorphism : SNP, mutations, diseases OMIM 602221 [ map ] GENECLINICS 602221

SNP ZNF198 [dbSNP-NCBI]

SNP NM_003453 [SNP-NCI]

SNP NM_197968 [SNP-NCI]

SNP ZNF198 [GeneSNPs - Utah] ZNF198 [SNP - CSHL] ZNF198] [HGBASE - SRS] General knowledge

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 178 - Family ZNF198 [UCSC Family Browser] Browser SOURCE NM_003453 SOURCE NM_197968 SMD Hs.507433 SAGE Hs.507433 Amigo component|nucleus Amigo process|regulation of transcription, DNA-dependent Amigo function|zinc ion binding PubGene ZNF198 Other databases Probes Probe Cancer Cytogenetics (Bari) Probe FIM Related clones (RZPD - Berlin) PubMed PubMed 8 Pubmed reference(s) in LocusLink

Bibliography Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13). Popovici C, Adelaide J, Ollendorff V, Chaffanet M, Guasch G, Jacrot M, Leroux D, Birnbaum D, Pebusque MJ Proc Natl Acad Sci U S A 1998 May 12;95(10):5712-7 Medline 98245146

The t(8;13)(p11;q11-12) rearrangement associated with an atypical myeloproliferative disorder fuses the fibroblast growth factor receptor 1 gene to a novel gene RAMP. Smedley D, Hamoudi R, Clark J, Warren W, Abdul-Rauf M, Somers G, Venter D, Fagan K, Cooper C, Shipley J. Hum Mol Genet 1998 Apr;7(4):637-42

FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome. Xiao S, Nalabolu SR, Aster JC, Ma J, Abruzzo L, Jaffe ES, Stone R, Weissman SM, Hudson TJ, Fletcher JA Nat Genet 1998 Jan;18(1):84-7 Medline 98085877

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 179 - Characterization of FIM-FGFR1, the fusion product of the myeloproliferative disorder-associated t(8;13) translocation. Ollendorff V, Guasch G, Isnardon D, Galindo R, Birnbaum D, Pébusque MJ. J Biol Chem 1999 Sep 17;274(38):26922-30.

ZNF198-FGFR1 transforming activity depends on a novel proline-rich ZNF198 oligomerization domain. Xiao S, McCarthy JG, Aster JC, Fletcher J. Blood 2000 Jul 15;96(2):699-704

REVIEW articles automatic search in PubMed Last year automatic search in PubMed publications

BiblioGene - INIST

Contributor(s) Written 03-1998 Jean-Loup Huret, Dominique Leroux Updated 01-2001 Marie-Joséphe Pébusque Citation This paper should be referenced as such : Huret JL, Leroux D . FIM (fused in myeloproliferative disorders).. Atlas Genet Cytogenet Oncol Haematol. March 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/ZNF198ID114.html Pébusque MJ . FIM (fused in myeloproliferative disorders).. Atlas Genet Cytogenet Oncol Haematol. January 2001 . URL : http://www.infobiogen.fr/services/chromcancer/Genes/ZNF198ID114.html

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t(9;12)(p24;p13)

Clinics and Pathology Disease acute leukaemias; poorly known: only 3 available cases, and with different phenotypes: a T-cell ALL, a CD10+-ALL, and a 'CML-like' disease in transformation; all 3 were male patients Genes involved and Proteins Gene Name JAK2 Location 9p24 Dna / Rna 24 exons Protein tyrosine kinase; possibly membrane associated; signal transduction Gene Name ETV6 Location 12p13 Dna / Rna 9 exons; alternate splicing Protein contains a Helix-Loop-Helix and ETS DNA binding domains; wide expression; nuclear localisation; ETS-related transcription factor. Result of the chromosomal anomaly

Hybrid gene

Description 5' ETV6 - 3' JAK2

Fusion Protein

Description N-term- HLH oligomerization domain from ETV6 fused to the tyrosine kinase c-term domains of JAK2 (or even starting with the JH2); the reciprocal JAK2-ETV6 may not be expressed Oncogenesis it may be speculated that the HLH domain of ETV6 induces oligomerization, resulting in constitutive activation of the kinase domain of

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 181 - JAK2

External links Other t(9;12)(p24;p13) Mitelman database (CGAP - NCBI) database Other t(9;12)(p24;p13) CancerChromosomes (NCBI) database To be noted Additional cases are needed to delineate the epidemiology of this rare entity: you are welcome to submit a paper to our new Case Report section. Bibliography Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P, Monpoux F, Van Rompaey L, Baens M, Van den Berghe H, Marynen P Blood 1997 Oct 1;90(7):2535-40 Medline 97465498

A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffe M, Berthou C, Lessard M, Berger R, Ghysdael J, Bernard OA Science 1997 Nov 14;278(5341):1309-12 Medline 98028754

Contributor(s) Written 02-1998 Jean-Loup Huret Citation This paper should be referenced as such : Huret JL . t(9;12)(p24;p13). Atlas Genet Cytogenet Oncol Haematol. February 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Anomalies/1122t0912.html

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 182 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

del(9q) solely

Identity Note del(9q) as the sole abnormality must be distinguished from syndromes where it is associated with other chromosome rearrangements; in particular, there is frequent association with LAM2 expressing t(8 ;21)(q22;q22), and, also, with t(15;17)(q24;q21); we herein describe del(9q) as the sole anomaly, when not otherwise specified

del(9)(q22q32) G- banding - Courtesy Jean-Luc Lai

Clinics and Pathology Disease ANLL mainly; rarely observed in myelodysplastic syndroms (MDS) or myeloproliferative disorders; biphenotypic T-lymphoid / myeloid leukemias cases have also been described Phenotype / ANLL: M1, M2, M4, M6 FAB subtypes; pluripotent stem cell probably cell stem involved; there is a trilineage myelodysplasia; six patients (4 M1, 1 M2 origin and 1 T-ALL) from two reports have been described with del(9q) and CD34+, CD7+, T lymphoid / myeloid biphenotypic leukemia. Epidemiology represented; adults and children may be affected Cytology frequent sideroblasts; leukemic blasts are agranular, with large vacuoles on Giemsa staining and localized positivity for myeloperoxydase (MPO); giant MPO positive granules are described, corresponding to =AB pseudo-Chediak-Higashi =BB granules; most blast cells are CD34 positive Prognosis when del(9q) is the unique chromosome abnormality the prognosis, depending on AML subtype, is variable; (del(9q) as a secondary anomaly in t(8;21) has no prognostic consequence for some workers and is a factor of worse prognosis for others) Cytogenetics

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 183 - Cytogenetics interstitial deletion of chromosome 9 long arm, called del(9q) or 9q-, Morphological involving a variable chromosome segment; the region 9q21-22 seems constantly involved Cytogenetics this constantly deleted region has not yet been more precisely defined Molecular and it is not known whether deletion of one or more critical gene(s) are be involved. Thus there are presently no 9q molecular probes availaible to assess 9q deletion Probes whole chromosome 9 painting, to exclude 9q translocations Additional on 31 reviewed cases of ANLL with del(9q) as a primary change, none anomalies had additional anomalies del(9q) as a secondary anomaly: - association with t(8 ;21) represents the majority of cases; t(8 ;21) occurs in 5 to 10 % of patients with ANLL, and its association with del(9q) is the second more frequent, after the association with loss of one sex chromosome; it represents approximatly 10-15 % of cases - association with t(15 ;17), in promyelocytic leukemia, has also seldom (1%) been observed - in these two syndromes, del(9q) is usually not present at diagnosis but appears as an additional change at relapse - del(9q) has never been described in association with other recurrent primary changes Variants unbalanced translocations involving 9q may, in a way, be considered as del(9q) variants. Genes involved and Proteins Note genes involved are unknown; there is probable deletion of one or several tumor suppressor gene(s) involved in the progression of the disease.

External links Other del(9q) solely Mitelman database (CGAP - NCBI) database Bibliography Interstitial 9q deletion in T-lymphoid/myeloid biphenotypic leukaemia. Akashi K, Shibuya T, Harada M, Oogami A, Teshima T, Takamatsu Y, Kikuchi M, Niho Y Br J Haematol. 1992 Feb;80(2):172-7. Medline 92198792

Interstitial 9q deletion is associated with CD7+ acute leukemia of myeloid and T lymphoid lineage. Ferrara F, Scognamiglio M, Di Noto R, Schiavone EM, Poggi V, Fiorillo A, Libertini R, Vicari L, Del Vecchio L, Sebastio L Leukemia. 1996 Dec;10(12):1990-2. Medline 97102702

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 184 - A subtype of the prototypic karyotype in acute myeloid leukemia t (8; 21) (q22; q22), del 9 (q13; q23). Hossfeld DK, Higi M, Kohler S, Miller A, Zschaber R Blut. 1980 Jan;40(1):27-32 Medline 80110148

Cytological features of 9q- deletions in AML. Hoyle C, Sherrington PD, Hayhoe FG Br J Haematol 1987 Jun;66(2):277-8 Medline 87271503

Secondary chromosomal abnormalities in acute leukemias. Johansson B, Mertens F, Mitelman F Leukemia. 1994 Jun;8(6):953-62. Medline 94268146

Interstitial 9q deletion (q12q22) in two cases of acute myeloblastic leukemia. Kao YS, Sartin BW, Van Brunt J, Hew AY Jr Cancer Genet Cytogenet. 1986 Jan 15;19(3-4):365-6 Medline 86105802

Specific minor chromosome deletions in myelodysplastic syndromes: clinical and morphologic correlations. Kerndrup G, Pedersen B, Bendix-Hansen K Cancer Genet Cytogenet. 1987 Jun;26(2):227-34 Medline 87187080

Interstitial deletion of 9q in a case of acute myeloid leukemia. Kwong YL, Ha SY, Liang RH, Wan TS, Chan LC Cancer Genet Cytogenet. 1993 Mar;66(1):79-80 Medline 93223172

Interstitial 9q- and dyserythropoiesis in acute myeloid leukemia. Kwong YL Am J Hematol. 1995 Jan;48(1):63-4 Medline 95133594

Interstitial deletion of the long arm of chromosome 9 as the sole anomaly in acute myeloid leukaemia is associated with dyserythropoiesis. Kwong YL, Chan TK, Chan LC Leukemia. 1992 Jan;6(1):64-5 Medline 92139938

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Interstitial 9q- deletion in a case of acute myeloid leukemia-M2 arising from a granulocytic sarcoma. Lunde JH, Allen EF Cancer Genet Cytogenet. 1994 Dec;78(2):239-41 Medline 95129069

Interstitial 9q- deletions in hematologic malignancies Mecucci C, Vermaelen K, Kulling G, Michaux JL, Noens L, Van Hove W, Tricot G, Louwagie A, Van den Berghe H Cancer Genet Cytogenet. 1984 Aug;12(4):309-19. Medline 84258959

Acute nonlymphocytic leukemia following lung cancer in a patient with a constitutional supernumerary chromosome. Minamihisamatsu M, Gregorio JS, Onozawa Y, Ishihara T Cancer Genet Cytogenet. 1988 Oct 15;35(2):263-8. Medline 89028225

6p+ and 9q- in two chromosomally distinct clones occurring in a case of myelodysplastic syndrome evolving to acute nonlymphocytic leukemia. Ringressi A, Mecucci C, Grossi A, Bernabei PA, Ferrini PR, Van den Berghe H Cancer Genet Cytogenet. 1988 Oct 15;35(2):213-21. Review Medline 89028219

Fifty-one patients with acute myeloid leukemia and translocation t(8;21)(q22;q22): an additional deletion in 9q is an adverse prognostic factor. Schoch C, Haase D, Haferlach T, Gudat H, Buchner T, Freund M, Link H, Lengfelder E, Wandt H, Sauerland MC, Loffler H, Fonatsch C Leukemia. 1996 Aug;10(8):1288-95 Medline 96320601

A new case of de novo AML with 9q interstitial deletion as the sole chromosomal abnormality. Smadja N, Krulik M, de Gramont A, Gonzalez G, Debray CJ Br J Haematol. 1987 Dec;67(4):494-5. Medline 88107463

Involvement of bands 9q21-q22 in five cases of acute nonlymphocytic leukemia. Sreekantaiah C, Baer MR, Preisler HD, Sandberg AA Cancer Genet Cytogenet. 1989 May;39(1):55-64. Medline 89275023

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 186 - Contributor(s) Written 02-1998 Franck Viguié Citation This paper should be referenced as such : Viguié F . del(9q) solely. Atlas Genet Cytogenet Oncol Haematol. February 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Anomalies/del9q.html

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Idiopathic thrombocythemia Essential thrombocythemia

Clinics and Pathology Disease chronic myeloproliferative syndrome Phenotype / cell stem pluripotent stem cell is involved origin Epidemiology annual incidence is less than 1/106; sex ratio: 1M/1F; median age 50-60 yrs. Clinics often revealed by haemorrhages or thrombosis; splenomegaly is found in 50% of cases; blood data: the disease is defined by a thrombocytosis > 600 X 109/l; the platelets count is actually often > 1000 X 109/l. Prognosis evolution: chronic disease; can evolve towards polycytemia vera or myelofibrosis, seldom towards ANLL; prognosis: often fair, is variable according to age and depends on haemorrhages, thromboses, and embolisms, which are the major causes of death in this disease. Cytogenetics Cytogenetics a normal karyotype is found in 95% of cases; +9 is the only anomaly Morphological having been described in as far as 4 cases! Genes involved and Proteins Note genes involved are unkown

To be noted 'Ph-positive thrombocythemia' are simply cases of CML with high thrombocytosis Bibliography Report on essential thrombocythemia [No authors listed] Cancer Genet Cytogenet. 1981 Oct;4(2):138-42 Medline 82136696

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Trisomy 9 in hematologic disorders: possible association with primary thrombocytosis. Cournoyer D, Noel P, Schmidt MA, Dewald GW Cancer Genet Cytogenet. 1987 Jul;27(1):73-8 Medline 87215554

Karyotypic patterns in chronic myeloproliferative disorders: report on 74 cases and review of the literature. Mertens F, Johansson B, Heim S, Kristoffersson U, Mitelman F Leukemia. 1991 Mar;5(3):214-20. Review Medline 91194326

Contributor(s) Written 08-1997 Jean-Loup Huret Updated 02-1998 Jean-Loup Huret Citation This paper should be referenced as such : Huret JL . Idiopathic thrombocythemia,Essential thrombocythemia. Atlas Genet Cytogenet Oncol Haematol. August 1997 . URL : http://www.infobiogen.fr/services/chromcancer/Anomalies/ET.html Huret JL . Idiopathic thrombocythemia,Essential thrombocythemia. Atlas Genet Cytogenet Oncol Haematol. February 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Anomalies/ET.html

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Acute basophilic leukemia t(X;6)(p11;q23)

Clinics and Pathology Disease rare type of acute myeloid leukemia Phenotype / cell stem basophilic precursor origin Epidemiology very rare but might be prominent in infants Clinics hyperhistaminemia syndrome has been reported in some of the cases Cytology major component of undifferentiated blasts + minor component of basophilic blasts (blasts containing large granules reacting positively to toluidine blue staining). Treatment ANLL protocols Prognosis good response to standard therapy for chilhood ANLL

Cytogenetics Cytogenetics t(X;6)(p11;q23) Morphological Cytogenetics not done Molecular

Genes involved and Proteins Note are unknown

External links Other t(X;6)(p11;q23) Mitelman database (CGAP - NCBI) database Other t(X;6)(p11;q23) CancerChromosomes (NCBI) database

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Bibliography Acute basophilic leukaemia and translocation t(X;6)(p11;q23) Dastugue N, Duchayne E, Kuhlein E, Rubie H, Demur C, Aurich J, Robert A, Sie P Br J Haematol. 1997 Jul;98(1):170-6 Medline 97376810

Contributor(s) Written 02-1998 Nicole Dastugue Citation This paper should be referenced as such : Dastugue N . Acute basophilic leukemia,t(X;6)(p11;q23). Atlas Genet Cytogenet Oncol Haematol. February 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Anomalies/LAbaso1124.html

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t(5;14)(q33;q32) PDGFRB/TRIP11

Clinics and Pathology Disease yet poorly known: 1 case of ANLL Clinics found at relapse with eosinophilia of a M2 ANLL with t(7;11) Cytogenetics Cytogenetics so far found as an additional anomaly in a clone bearing a Morphological t(7;11)(p15;p15) Genes involved and Proteins Gene Name PDGFRB Location 5q33 Protein PDGFRB is the receptor for PDGFB (platelet-derived growth factor-b); membrane protein; belongs to the immunoglobulin superfamily Gene Name CEV14 Location 14q32 Protein contains a N-term leucine zipper and a C-term putative thyroid hormone receptor interacting domain Result of the chromosomal anomaly

Hybrid gene

Description 5' CEV14 - 3' PDGFRb Transcript 10 kb fusion transcript (major) and other (minor) transcripts

Fusion Protein

Description N-term leucine zipper from CEV14 fused to the transmembrane domain andtheTyrkinasedomainofPDGFRbinC-term; the reciprocal transcript

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 192 - is not expressed; breakpoints at amino acids 1936 of PDGFRb and 567 of CEV14 Oncogenesis ectopic constitutive tyrosine kinase activation of PDGFRb may occur

External links Other t(5;14)(q33;q32) Mitelman database (CGAP - NCBI) database Other t(5;14)(q33;q32) CancerChromosomes (NCBI) database To be noted the above t(5;14)(q33;q32) with PDGFRb and CEV14 rearrangements must not be confused with the t(5;14)(q31;q32) with IL3 and IgH involvements found in ALL. Bibliography Acute myeloblastic leukemia (M2) with translocation (7;11) followed by marked eosinophilia and additional abnormalities of chromosome 5. Abe A, Tanimoto M, Towatari M, Matsuoka A, Kitaori K, Kato H, Toyozumi H, Takeo T, Adachi K, Emi N, et al Cancer Genet Cytogenet. 1995 Aug;83(1):37-41 Medline 95384961

Fusion of the platelet-derived growth factor receptor beta toa novel gene CEV14 in acute myelogenous leukemia after clonal evolution. Abe A, Emi N, Tanimoto M, Terasaki H, Marunouchi T, Saito H Blood. 1997 Dec 1;90(11):4271-7. Medline 98043615

Contributor(s) Written 02-1998 Jean-Loup Huret Citation This paper should be referenced as such : Huret JL . t(5;14)(q33;q32). Atlas Genet Cytogenet Oncol Haematol. February 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Anomalies/t0514ANL.html

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t(11;16)(q23;p13)

Clinics and Pathology Disease ANLL/MDS: only treatment related leukaemias cases so far (in other 11q23 translocations, most cases occur in de novo acute leukemia) Phenotype / M4, M2 ANLL; CMML and RAEBT, although MDS is otherwise rarely cell stem seen in 11q23 translocations; the fusion gene is found in all the mature origin monocytes, in some of the granulocytes and erythroblasts, not in the lymphocytes Epidemiology 13 available cases; most cases are children cases: median age is 10-14 yrs, range is 2-74 yrs; sex ratio is balanced Clinics secondary to antitopoisomerase II drugs (etoposide or teniposide, but also doxorubicin); this secondary malignancy occurs within 6-60 mths (median 20 mths); the primary malignancy was a t(8;21)(q22;q22)/M2-ANLL in 2 cases Prognosis yet unknown

Cytogenetics Additional are found in 8 of 11 cases; variable, except the unexpectected recurrence anomalies of 1p36.1 involvement

Genes involved and Proteins Gene Name MLL Location 11q23 Dna / Rna 21 exons, spanning over 100 kb; 13-15 kb mRNA Protein 431 kDa; contains two DNA binding motifs (a AT hook, and Zinc fingers), a DNA methyl transferase motif, a bromodomain; transcriptional regulatory factor; nuclear localisation Gene Name CBP Location 16p13 Protein nuclear localisation; transcriptional adaptor/coactivator: binds CREB; has histone acetyltransferase activity

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 194 -

Result of the chromosomal anomaly

Hybrid gene

Description 5' MLL - 3'CBP

Fusion Protein

Description N-term AT hook and DNA methyltransferase from MLL fused to most of CBP starting with the bromodomain of CBP -or even more in N-term with the CREB binding domain- and also comprising the cystein/histidine rich and the glutamine rich domains of CBP in C-term around 1400 amino acids from MLL; the reciprocal CBP-MLL may or may not be expressed Oncogenesis may promote histone acetylation of genomic regions targeted by the MLL AT-hooks; may loose CBP cell cycle inhibition capability

External links Other t(11;16)(q23;p13) Mitelman database (CGAP - NCBI) database Other t(11;16)(q23;p13) CancerChromosomes (NCBI) database

Bibliography Novel MLL-CBP fusion transcript in therapy-related chronic myelomonocytic leukemia with a t(11;16)(q23;p13) chromosome translocation. Satake N, Ishida Y, Otoh Y, Hinohara S, Kobayashi H, Sakashita A, Maseki N, Kaneko Y Genes Chromosomes Cancer. 1997 Sep;20(1):60-3. Medline 97436288

The t(11;16)(q23;p13) translocation in myelodysplastic syndrome fuses the MLL gene to the CBP gene. Taki T, Sako M, Tsuchida M, Hayashi Y Blood. 1997 Jun 1;89(11):3945-50 Medline 97309416

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 195 - All patients with the T(11;16)(q23;p13.3) that involves MLL and CBP have treatment-related hematologic disorders. Rowley JD, Reshmi S, Sobulo O, Musvee T, Anastasi J, Raimondi S, Schneider NR, Barredo JC, Cantu ES, Schlegelberger B, Behm F, Doggett NA, Borrow J, Zeleznik-Le N Blood. 1997 Jul 15;90(2):535-41. Medline 97369711

MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3). Sobulo OM, Borrow J, Tomek R, Reshmi S, Harden A, Schlegelberger B, Housman D, Doggett NA, Rowley JD, Zeleznik-Le NJ Proc Natl Acad Sci U S A 1997 Aug 5;94(16):8732-7 Medline 97385172

Contributor(s) Written 02-1998 Jean-Loup Huret Citation This paper should be referenced as such : Huret JL . t(11;16)(q23;p13). Atlas Genet Cytogenet Oncol Haematol. February 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Anomalies/t1116.html © Atlas of Genetics and Cytogenetics in Oncology and Haematology

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 196 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

t(16;21)(p11;q22) (updated: old version not available)

Clinics and Pathology Disease de novo acute non lymphocytic leukemia (ANLL); to be noted is one case of chronic myelogenous leukemia (CML) -blast crisis. Phenotype / ANLL cases: mainly M1, M2, M4, M5a, M5b, or M7 ANLL; may be cell stem preceded by a myelodysplastic syndrome (MDS). origin Epidemiology about 40 reported cases, mainly found in young adults; children cases are described; median age is about 30 yrs; balanced sex ratio Clinics blood data: anemia, thrombocytopenia, mild hyperleucocytosis; with high monocytic cell count at times Cytology myelocytic and monocytoid features are often present; eosinophils in the bone marrow are sometimes abnormal and/or elevated; erythrophagocytosis may be found Prognosis seems poor: complete remission may not be achieved; there is high incidence of relapse within a year and a median of survival is about 22 months (cases herein reviewed)

Disease Ewing tumours Note t(16;21)(p11;q22) has been found in rare cases of Ewing tumours, a paediatric neoplasm with small round-cells derived from neural crests cells usually associated with translocations involving EWSR1 Cytogenetics Ewing tumours are usually associated with a t(11;22)(q24;q12) with 5' EWSR1 - 3' FLI1 involvement, less often associated with t(21;22)(q22;q12) with 5' EWSR1 - 3' ERG involvement, rarely associated with t(2;22)(q36; q12) (5' EWSR1 - 3' FEV) or with t(17;22)(q21;q12) (5' EWSR1-3' ETV4) Prognosis recent treatments have improved the prognosis of Ewing's tumours. The prognosis is mainly determined by the presence of metastases at the time of diagnosis

Cytogenetics

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 197 - Additional ANLL cases: found solely in about 60% of cases in at least a subclone; anomalies associated with +10, +8, or de(9q)/-9 in about 10% of cases each

Genes involved and Proteins Gene Name FUS Location 16p11 Protein RNA binding protein; member of the TET family, like EWSR1 Gene Name ERG Location 21q22 Protein ETS transcription factor

Result of the chromosomal anomaly

Hybrid gene

Description 5' FUS including exons 1 to 6, 7 or 8 - 3' ERG from exon 7, 8 or 9 to C- term.

Fusion Protein

Description N-term FUS transactivation domain fused to the C-term DNA binding ETS domain of ERG Oncogenesis seems to act as a transcriptional activator

External links Other t(16;21)(p11;q22) Mitelman database (CGAP - NCBI) database Other t(16;21)(p11;q22) CancerChromosomes (NCBI) database

Bibliography

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 198 - Acute nonlymphoblastic leukemia with bone marrow eosinophilia and structural anomaly of chromosome 16. Mecucci C, Bosly A, Michaux JL, Broeckaert-Van Orshoven A, Van den Berghe H Cancer Genet Cytogenet. 1985; 17: 359-363. Medline 85254357

Translocation (8;21) and its variants in acute nonlymphocytic leukemia. The relative importance of chromosomes 8 and 21 to the genesis of the disease. Minamihisamatsu M, Ishihara T. Cancer Genet Cytogenet. 1988; 33: 161-173. Medline 3164243

Acute nonlymphocytic leukemia with t(16;21) Berkowicz M, Rosner E, Resnitzky P, Mamon Z, Ben-Bassat I, Ramot B Cancer Genet Cytogenet. 1990; 47: 139-140 Medline 2357684

16;21 translocation in acute nonlymphocytic leukemia with abnormal eosinophils: a unique subtype. Sadamori N, Yao E, Tagawa M, Nakamura H, Sasagawa I, Itoyama T, Tokunaga S, Ichimaru M, Nakamura I, Kamei T, et al. Acta Haematol. 1990; 84: 212-216. Medline 2125791

Translocation (16;21)(p11;q22) in acute monoblastic leukemia with erythrophagocytosis. Marosi C, Bettelheim P, Geissler K, Lechner K, Koller U, Haas OA, Chott A, Hagemeijer A. Cancer Genet Cytogenet. 1991; 54: 61-66. Medline 2065316 t(16;21)(p11.2;q22): a recurrent primary rearrangement in ANLL. Morgan R, Riske CB, Meloni A, Ries CA, Johnson CH, Lemons RS, Sandberg AA. Cancer Genet Cytogenet. 1991; 53: 83-90. Medline 2036642 t(16;21) in a Ph positive CML. Ferro MR, Cabello P, Garcia-Sagredo JM, Resino M, San Roman C, Larana JG. Cancer Genet Cytogenet. 1992; 60:210-211. No abstract available. Medline 1606569

The 8;21 chromosome translocation in acute myeloid leukemia is always detectable by molecular analysis using AML1.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 199 - Maseki N, Miyoshi H, Shimizu K, Homma C, Ohki M, Sakurai M, Kaneko Y. Blood. 1993; 81: 1573-1579. Medline 8453103

Acute non-lymphocytic leukemia with t(16;21). Nobbs MC, Chan-Lam D, Howell RT, Kitchen C, Copplestone JA. Cancer Genet Cytogenet. 1993 ;70: 144-145. Review. Medline 8242597

Translocation (16;21)(p11;q22) in acute nonlymphocytic leukemia. Okada K, Takeichi M, Uchida H, Shirota T, Sakai N, Ito H. Cancer Genet Cytogenet. 1994; 75: 60-63. Medline 8039166

Fusion of the FUS gene with ERG in acute myeloid leukemia with t(16;21)(p11;q22). Panagopoulos I, Aman P, Fioretos T, Hoglund M, Johansson B, Mandahl N, Heim S, Behrendtz M, Mitelman F. Genes Chromosomes Cancer. 1994; 11: 256-262. Medline 7533529

[Acute monoblastic leukemia (M5a) with dysmegakaryocytopoiesis associated with t(16;21) (p11;q22)] Satoh K, Miura I, Chubachi A, Ohtani H, Hirokawa M, Niitsu H, Miura AB. Rinsho Ketsueki. 1994; 35: 160-164. Review. Japanese. Medline 8139114

HLA-DR-, CD33+, CD56+, CD16- myeloid/natural killer cell acute leukemia: a previously unrecognized form of acute leukemia potentially misdiagnosed as French-American-British acute myeloid leukemia-M3 Scott AA, Head DR, Kopecky KJ, Appelbaum FR, Theil KS, Grever MR, Chen IM, Whittaker MH, Griffith BB, Licht JD, et al.. Blood. 1994; 84: 244-255. Medline 7517211

Acute non-lymphoblastic leukaemia with t(16;21): case report with a review of the literature. Hiyoshi M, Koh KR, Yamane T, Tatsumi N Clin Lab Haematol 1995; 17: 243-246. Medline 96318536

Establishment and characterization of IRTA17 and IRTA21, two novel acute nonlymphocytic leukaemia cell lines with t(16;21) translocation.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 200 - Hiyoshi M, Yamane T, Hirai M, Tagawa S, Hattori H, Nakao Y, Yasui Y, Koh KR, Hino M, Tatsumi N. Br J Haematol. 1995; 90: 417-424. Medline 7794765

Detection of minimal residual disease in cerebro-spinal fluid of a patient with acute myelogenous leukemia with t(16;21)(p11;q22) translocation by reverse transcriptase-polymerase chain reaction. Harigae H, Kobayashi M, Mihara A, Watanabe N. Tohoku J Exp Med. 1997; 183: 297-302. Medline 9549830

Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript. Kong XT, Ida K, Ichikawa H, Shimizu K, Ohki M, Maseki N, Kaneko Y, Sako M, Kobayashi Y, Tojou A, Miura I, Kakuda H, Funabiki T, Horibe K, Hamaguchi H, Akiyama Y, Bessho F, Yanagisawa M, Hayashi Y. Blood. 1997; 90: 1192-1199. Medline 9242552

Cytogenetic analysis of de novo acute myeloid leukemia with trilineage myelodysplasia in comparison with myelodysplastic syndrome evolving to acute myeloid leukemia. Tamura S, Takemoto Y, Hashimoto-Tamaoki T, Mimura K, Sugahara Y, Senoh J, Furuyama JI, Kakishita E. Int J Oncol. 1998; 12: 1259-1262. Medline 9592183

Hemophagocytosis by leukemic blasts in a case of acute megakaryoblastic leukemia with t(16;21)(p11;q22). Imashuku S, Hibi S, Kuriyama K, Todo S. Int J Hematol. 1999; 70: 36-39. Medline 10446493

Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a cooperative pediatric oncology group study-POG 8821. Raimondi SC, Chang MN, Ravindranath Y, Behm FG, Gresik MV, Steuber CP, Weinstein HJ, Carroll AJ. Blood. 1999; 94: 3707-3716. Medline 10572083

Myeloid differentiation antigen and cytokine receptor expression on acute

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 201 - myelocytic leukaemia cells with t(16;21)(p11;q22): frequent expression of CD56 and interleukin-2 receptor alpha chain. Shikami M, Miwa H, Nishii K, Takahashi T, Shiku H, Tsutani H, Oka K, Hamaguchi H, Kyo T, Tanaka K, Kamada N, Kita K. Br J Haematol. 1999; 105: 711-719. Medline 10354136

Acute myeloid leukemia possessing jumping translocation is related to highly elevated levels of EAT/mcl-1, a Bcl-2 related gene with anti-apoptotic functions. Okita H, Umezawa A, Fukuma M, Ando T, Urano F, Sano M, Nakata Y, Mori T, Hata J. Leuk Res. 2000; 24: 73-77. Medline 10634649

Cytogenetic profile of childhood and adult megakaryoblastic leukemia (M7): a study of the Groupe Francais de Cytogenetique Hematologique (GFCH). Dastugue N, Lafage-Pochitaloff M, Pages MP, Radford I, Bastard C, Talmant P, Mozziconacci MJ, Leonard C, Bilhou-Nabera C, Cabrol C, Capodano AM, Cornillet- Lefebvre P, Lessard M, Mugneret F, Perot C, Taviaux S, Fenneteaux O, Duchayne E, Berger R; Groupe Francais d'Hematologie Cellulaire. Blood. 2002; 100: 618-626. Medline 12091356

FUS/ERG gene fusions in Ewing's tumors. Shing DC, McMullan DJ, Roberts P, Smith K, Chin SF, Nicholson J, Tillman RM, Ramani P, Cullinane C, Coleman N. Cancer Res. 2003; 63: 4568-4576. Medline 12907633

Breakpoint differentiation in chromosomal aberrations of hematological malignancies: Identification of 33 previously unrecorded breakpoints. Heller A, Loncarevic IF, Glaser M, Gebhart E, Trautmann U, Claussen U, Liehr T. Int J Oncol. 2004; 24: 127-136. Medline 14654949

Contributor(s) Written 02-1998 Christine Pérot Updated 01-2005 Jean Loup Huret Citation This paper should be referenced as such : Pérot C . t(16;21)(p11;q22). Atlas Genet Cytogenet Oncol Haematol. February 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Anomalies/t1621.html

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 202 - Huret JL . t(16;21)(p11;q22). Atlas Genet Cytogenet Oncol Haematol. January 2005 . URL : http://www.infobiogen.fr/services/chromcancer/Anomalies/t1621.html © Atlas of Genetics and Cytogenetics in Oncology and Haematology

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 203 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

Neuroblastoma

Identity Note belongs to the group of 'small blue round cell' tumours of the children, and differential diagnosis with primitive neurectodermal tumours (PNET), lymphoma, Ewing's tumour, and rhabdomyosarcoma may be difficult. Clinics and Pathology Disease tumour of the sympathetic nervous system: medulloadrenal gland (50%), abdominal (25%) thoracic (15%), cervical or pelvic paraspinal ganglia; metastatic at diagnosis in 60% of cases (lymph nodes, bones and bone marrow, liver, skin) Embryonic neural crest cells origin Etiology unknown; possible excess in neurofibromatosis type I, Wiedemann- Beckwith syndrome, and maternal exposure to phenyl hydantoin; exceptional familial cases Epidemiology incidence is 5-10 per million children per yr; 10% of cancers in childhood; half cases by the age of 2 yrs, 90% before 6 yrs Clinics presenting signs are according to the localization of the tumoural mass; high catecholamin excretion Pathology tumours may exhibit various degrees of differentiation: neuroblastoma: undifferentiated cells that may be arranged in rosettes surrounding a fibrillar centre; 2 - ganglioneuroblastoma: presenting with more fibrillar material and a mixture of the above described with >50% of more mature cells, those found in 3 - ganglioneuroma, composed of well differentiated ganglion cells and Schwann cells; a given tumour may contain more and less mature cell areas staging (Evans): stage I: confined to the organ or structure of origin stage II: extending beyond the organ, but not crossing the midline (e.g. homolateral lymph nodes may be involved) stage III: extending and crossing the midline stage IV: distant metastases stage IVs: stage I or II otherwise in children aged <1 yr, with metastases in: liver, skin, bone marrow, but not in the bones Treatment surgery and/or radiation therapy, and/or chemotherapy

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 204 - Evolution spontaneous (and treatment induced) regression or differenciation into benign cells (ganglioneuroma) occur in rare cases (mainly in infant cases) Prognosis prognosis is very poor in most cases (median survival 1 yr); good outcome (90%) only for patients with lymph nodes negative for tumour (POG stage A); younger patients have better outcome than older patients; cytogenetic and genetic anomalies are of important prognostic value (see below) Genetics Note heterogenous disease from the genetic viewpoint; 90% cases exhibit genetic abnormalities Cytogenetics Cytogenetics two types can be delineated according to ploidy: Morphological aneuploid tumours (near triploid, pentaploid or hexaploid), with whole chromosome anomalies, often with relative gains of chromosomes 17, 7, 6, relative losses of chromosomes 11, 14, X (molecular cytogenetics: detection with comparative genomic hybridization (CGH); these are low grade tumours, with good prognosis. diploid and/or tetraploid tumours, with del(1p) -minimal critical region being 1p36- in 40% cases, del(11q), partial trisomy for 17q21-qter (in 90% of high grade tumours), DM or HSR ( N-myc amplification); these anomalies are often associated, found in high grade tumours, and bear a grave prognosis. Genes involved and Proteins Gene Name NMYC Location 2p24 Protein nuclear protein; contains a helix-loop-helix and a leucine zipper; transcription factor Result of the chromosomal anomaly Fusion Protein Oncogenesis amplification of NMYC is found in various tumours, in particular neuroblastoma; the level of amplification increases with tumour progression

To be noted screening programs in several countries could not induce a fall in mortality

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 205 - Short references Evans AE et al. Cancer 1971; 27: 374. Shimada H et al. J Natl Cancer Inst 1984; 73: 405. Triche TJ. Pediatr Pathol 1990; 10: 175-193. (REVIEW). Look AT et al. J Clin Oncol 1991; 9: 581. Brodeur GM et al. Am J Pediatr Hematol Oncol 1992; 14: 111. Carlsen NLT. Am J Pediatr Hematol Oncol 1992; 14: 103. Caron H et al. Nature Genet 1993; 4: 187. Craft AW, Parker L. Eur J Cancer 1996; 32A: 1540. Meddeb M et al. Genes Chromosomes and Cancer 1996; 17: 156. Plantaz D et al. Am J Pathol 1997; 150: 81. External links Orphanet Neuroblastoma Full Bibliography A proposed staging for children with neuroblastoma. Children's cancer study group A Evans AE, D'Angio GJ, Randolph J Cancer. 1971 Feb;27(2):374-8 Medline 71104684

Histopathologic prognostic factors in neuroblastic tumors: definition of subtypes of ganglioneuroblastoma and an age-linked classification of neuroblastomas. Shimada H, Chatten J, Newton WA Jr, Sachs N, Hamoudi AB, Chiba T, Marsden HB, Misugi K J Natl Cancer Inst 1984 Aug;73(2):405-16 Medline 84268646

Neuroblastoma and other childhood neural tumors: a review Triche TJ Pediatr Pathol. 1990;10(1-2):175-93. Review. Medline 90192500

Clinical relevance of tumor cell ploidy and N-myc gene amplification i childhood neuroblastoma: a Pediatric Oncology Group study. Look AT, Hayes FA, Shuster JJ, Douglass EC, Castleberry RP, Bowman LC, Smith EI, Brodeur GM J Clin Oncol. 1991 Apr;9(4):581-91 Medline 91294826

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 206 - Molecular basis of clinical heterogeneity in neuroblastoma Brodeur GM, Nakagawara A Am J Pediatr Hematol Oncol. 1992 May;14(2):111-6. Review. Medline 92411391

Neuroblastoma: epidemiology and pattern of regression. Problems in interpreting results of mass screening Carlsen NL. Am J Pediatr Hematol Oncol. 1992 May;14(2):103-10. Review. Medline 92411390

Allelic loss of chromosome 1p36 in neuroblastoma is of preferential maternal origin and correlates with N-myc amplification. Caron H, van Sluis P, van Hoeve M, de Kraker J, Bras J, Slater R, Mannens M, Voute PA, Westerveld A, Versteeg R Nat Genet. 1993 Jun;4(2):187-90 Medline 93350639

Screening for neuroblastoma: 20 years and still no answer Craft AW, Parker L Eur J Cancer. 1996 Aug;32A(9):1540-3. Review Medline 97067767

Additional copies of a 25 Mb chromosomal region originating from 17q23.1-17qter are present in 90% of high-grade neuroblastomas Meddeb M, Danglot G, Chudoba I, Venuat AM, Benard J, Avet-Loiseau H, Vasseur B, Le Paslier D, Terrier-Lacombe MJ, Hartmann O, Bernheim A Genes Chromosomes Cancer. 1996 Nov;17(3):156-65 Medline 97101676

Gain of chromosome 17 is the most frequent abnormality detected in neuroblastoma by comparative genomic hybridization. Plantaz D, Mohapatra G, Matthay KK, Pellarin M, Seeger RC, Feuerstein BG Am J Pathol. 1997 Jan;150(1):81-9. Medline 97158984

REVIEW articles

Last year publications

Contributor(s)

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 207 - Written 02-1998 Jérome Couturier and Daniel Satgé Citation This paper should be referenced as such : Couturier J and Satgé D . Neuroblastoma. Atlas Genet Cytogenet Oncol Haematol. February 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Tumors/neurob5002.html

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 208 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

t(16;21)(p11;q22) in Ewing's tumours (updated: old version not available)

Clinics and Pathology Disease Ewing tumours Note t(16;21)(p11;q22) has been found in rare cases of Ewing tumours, a paediatric neoplasm with small round-cells derived from neural crests cells usually associated with translocations involving EWSR1 t(16;21)(p11;q22) is also a well known chromosome anomaly in acute non lymphocytic leukaemia Cytogenetics Ewing tumours are usually associated with a t(11;22)(q24;q12) with 5' EWSR1 - 3' FLI1 involvement, less often associated with t(21;22)(q22;q12) with 5' EWSR1 - 3' ERG involvement, rarely associated with t(2;22)(q36; q12) (5' EWSR1 - 3' FEV) or with t(17;22)(q21;q12) (5' EWSR1-3' ETV4 ) Prognosis recent treatments have improved the prognosis of Ewing's tumours. The prognosis is mainly determined by the presence of metastases at the time of diagnosis Cytogenetics

Genes involved and Proteins Gene Name FUS Location 16p11 Protein RNA binding protein; member of the TET family, like EWSR1

Gene Name ERG Location 21q22 Protein ETS transcription factor

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 209 - Result of the chromosomal anomaly Hybrid Gene Description 5' FUS including exons 1 to 6, 7 or 8 - 3' ERG from exon 7, 8 or 9 to C- term. Fusion

Protein Description N-term FUS transactivation domain fused to the C-term DNA binding ETS domain of ERG Oncogenesis seems to act as a transcriptional activator

Bibliography Acute nonlymphoblastic leukemia with bone marrow eosinophilia and structural anomaly of chromosome 16. Mecucci C, Bosly A, Michaux JL, Broeckaert-Van Orshoven A, Van den Berghe H Cancer Genet Cytogenet. 1985; 17: 359-363. Medline 85254357

Acute nonlymphocytic leukemia with t(16;21) Berkowicz M, Rosner E, Resnitzky P, Mamon Z, Ben-Bassat I, Ramot B Cancer Genet Cytogenet. 1990; 47: 139-140 Medline 2357684

Translocation (16;21)(p11;q22) in acute monoblastic leukemia with erythrophagocytosis. Marosi C, Bettelheim P, Geissler K, Lechner K, Koller U, Haas OA, Chott A, Hagemeijer

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 210 - A. Cancer Genet Cytogenet. 1991; 54: 61-66. Medline 2065316 t(16;21)(p11.2;q22): a recurrent primary rearrangement in ANLL. Morgan R, Riske CB, Meloni A, Ries CA, Johnson CH, Lemons RS, Sandberg AA. Cancer Genet Cytogenet. 1991; 53: 83-90. Medline 2036642 t(16;21) in a Ph positive CML. Ferro MR, Cabello P, Garcia-Sagredo JM, Resino M, San Roman C, Larana JG. Cancer Genet Cytogenet. 1992; 60:210-211. No abstract available. Medline 1606569

The 8;21 chromosome translocation in acute myeloid leukemia is always detectable by molecular analysis using AML1. Maseki N, Miyoshi H, Shimizu K, Homma C, Ohki M, Sakurai M, Kaneko Y. Blood. 1993; 81: 1573-1579. Medline 8453103

Acute non-lymphocytic leukemia with t(16;21). Nobbs MC, Chan-Lam D, Howell RT, Kitchen C, Copplestone JA. Cancer Genet Cytogenet. 1993 ;70: 144-145. Review. Medline 8242597

Translocation (16;21)(p11;q22) in acute nonlymphocytic leukemia. Okada K, Takeichi M, Uchida H, Shirota T, Sakai N, Ito H. Cancer Genet Cytogenet. 1994; 75: 60-63. Medline 8039166

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 211 -

Acute non-lymphoblastic leukaemia with t(16;21): case report with a review of the literature. Hiyoshi M, Koh KR, Yamane T, Tatsumi N Clin Lab Haematol 1995; 17: 243-246. Medline 96318536

Establishment and characterization of IRTA17 and IRTA21, two novel acute nonlymphocytic leukaemia cell lines with t(16;21) translocation. Hiyoshi M, Yamane T, Hirai M, Tagawa S, Hattori H, Nakao Y, Yasui Y, Koh KR, Hino M, Tatsumi N. Br J Haematol. 1995; 90: 417-424. Medline 7794765

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 212 - Medline 9592183

Hemophagocytosis by leukemic blasts in a case of acute megakaryoblastic leukemia with t(16;21)(p11;q22). Imashuku S, Hibi S, Kuriyama K, Todo S. Int J Hematol. 1999; 70: 36-39. Medline 10446493

Myeloid differentiation antigen and cytokine receptor expression on acute myelocytic leukaemia cells with t(16;21)(p11;q22): frequent expression of CD56 and interleukin-2 receptor alpha chain. Shikami M, Miwa H, Nishii K, Takahashi T, Shiku H, Tsutani H, Oka K, Hamaguchi H, Kyo T, Tanaka K, Kamada N, Kita K. Br J Haematol. 1999; 105: 711-719. Medline 10354136

FUS/ERG gene fusions in Ewing's tumors. Shing DC, McMullan DJ, Roberts P, Smith K, Chin SF, Nicholson J, Tillman RM, Ramani P, Cullinane C, Coleman N. Cancer Res. 2003; 63: 4568-4576.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 213 - Medline 12907633

REVIEW articles automatic search in PubMed Last year automatic search in PubMed publications Contributor(s) Written 02-1998 Christine Pérot Updated 01-2005 Jean Loup Huret Citation This paper should be referenced as such : Pérot C . t(16;21)(p11;q22). Atlas Genet Cytogenet Oncol Haematol. February 1998 . URL : http://AtlasGeneticsOncology.org/Tumors/t1621p11q22EwingID5329.html Huret JL . t(16;21)(p11;q22). Atlas Genet Cytogenet Oncol Haematol. January 2005 . URL : http://AtlasGeneticsOncology.org/Tumors/t1621p11q22EwingID5329.html

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 214 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

Bannayan-Riley-Ruvalcaba syndrome

Identity Other Bannayan-Zonana syndrome names Riley-Smith syndrome Ruvalcaba-Myhre-Smith syndrome Macrocephaly, pseudopapilledema, multiple hemangiomata Macrocephaly, multiple lipomas, hemangiomata Inheritance autosomal dominant; existence of sporadic cases Clinics Note Bannayan-Riley-Ruvalcaba syndrome is an overgrowth syndrome / hamartomatous polyposis condition with an increased risk of benign and malignant tumours; other overgrowth syndromes at (known) risk of tumourigenesis are : Beckwith-Weideman syndrome, Sotos syndrome (cerebral gigantism), Hemihyperplasia (hemihypertrophy), and Simpson Golabi Behemel syndrome. Phenotype onset in chilhood (in contrast with Cowden disease, although an allelic and clinics disorder, see below); more often found in male patients (lower penetrance in female patients). - overgrowth at birth (postnatal growth decelerates). - macrocephaly - hypotonia and mental deficiency - subcutaneous and visceral lipomas and hemangiomas, and intestinal juvenile polyposis. - myopathy of the proximal type in 2/3 of cases - pigmentation spots of the male genitalia Neoplastic multiple lipomas (75% of cases). risk hemangiomas (40%). hamartomatous polyps (ileus and colon; 45%). lymphangiomas (10%).

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 215 - Genes involved and Proteins

Gene Name PTEN Location 10q23 Protein Description 403 amino acids Function protein tyrosine phosphatase; tumour suppressor gene Mutations Germinal may be not all Bannayan-Riley-Ruvalcaba syndrome cases are due to PTEN mutations; germ-line mutations have also been described in Cowden disease and in some cases with juvenile polyposis syndrome. Somatic PTEN is mutated in a large number of cancer types

External links OMIM 153480 Orphanet Bannayan-Zonana syndrome HGMD 6022948 Bibliography Macrocephaly, pseudopapilledema and multiple hemangiomata: a previously undescribed heredofamilial syndrome. Riley HD Jr and Smith WR. Pediatrics 1960; 26: 293-300.

Lipomatosis, angiomatosis, and macrencephalia: a previously undescribed congenital syndrome. Bannayan GA. Arch Path 1971; 92: 1-5. Medline 71233629

Sotos syndrome with intestinal polyposis and pigmentary changes of the genitalia. Ruvalcaba RHA, Myhre S, Smith DW. Clin Genet 1980; 18: 413-416.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 216 - Medline 81088856

Deletion of PTEN in a patient with Bannayan-Riley-Ruvalcaba syndrome suggests allelism with Cowden disease. Arch EM, Goodman BK, Van Wesep RA, Liaw D, Clarke K, Parsons R, McKusick VA, Geraghty M. Am J Med Genet 1997; 71: 489-493. Medline 97432577

Germline mutations in PTEN are present in Bannayan-Zonana syndrome. Marsh DJ, Dahia PLM, Zheng Z, Liaw D, Parsons R, Gorlin RJ, Eng C. Nature Genet 1997; 16: 333-334. Medline 97385233

Absence of PTEN/MMAC1 germ-line mutations in sporadic Bannayan-Riley- Ruvalcaba syndrome. Carethers JM, Furnari FB, Zigman AF, Lavine JE, Jones MC, Graham GE, Teebi AS, Huang HJ, Ha HT, Chauhan DP, Chang CL, Cavenee WK, Boland CR Cancer Res 1998; 58: 2724-2726. Medline 98324258

Inherited macrocephaly-hamartoma syndromes. DiLiberti JH. Am J Med Genet 1998; 79: 284-290. Medline 98453170

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Marsh DJ, Coulon V, Lunetta KL, Rocca-Serra P, Dahia PL, Zheng Z, Liaw D, Caron S, Duboue B, Lin AY, Richardson AL, Bonnetblanc JM, Bressieux JM, Cabarrot-Moreau A, Chompret A, Demange L, Eeles RA, Yahanda AM, Fearon ER, Fricker JP, Gorlin RJ, Hodgson SV, Huson S, Lacombe D, Eng C, et al. Hum Mol Genet 1998; 7: 507-515. Medline 98133933

REVIEW articles automatic search in PubMed Last year automatic search in PubMed publications Contributor(s) Written 11-1998 Jean-Loup Huret Citation

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 217 - This paper should be referenced as such : Huret JL . Bannayan-Riley-Ruvalcaba syndrome. Atlas Genet Cytogenet Oncol Haematol. November 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Tumors/BannayanID10044.html

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 218 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

Bloom syndrome (updated: old version not available)

Identity Inheritance autosomal recessive; frequency is about 2/105 newborns in Ashkenazi Jews and in the Japanese (founder effect: affected persons descent from a common ancestor); much rarer otherwise

micronuclei (left); sister chromatid exchange (right) in a normal subject (herein: 19 SCE, instead of the hundred found in Bloom, see below) - Editor

Clinics Note 168 cases have been registered in the Bloom's syndrome Registry by James German; BS patients are predisposed to all types of cancer observed in the general population; thus, BS is a model of initiation and promotion of cancer, and highligths internal causes/processes of cancers Phenotype - phenotypic spectrum variable.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 219 - and clinics - growth : dwarfism: intrauterine growth retardation; birth weight: below 2.3 kg; mean length: 44 cm; adult length < 145 cm. - skin: hyperpigmented (cafÈ au lait) spots; hypopigmented areas; sun sensitive telangiectatic erythema; in butterfly configuration across the face: resembles lupus erythematous - head: microcephaly; dolichocephaly; narrow face; prominent nose and/or ears; characteristic high-pitched voice - normal intelligence - immune deficiency --> frequent infections (may be life-threatening) - other: myocardopathy; hypogonadism in male patients; hypertriglyceridemia Neoplastic nearly half of patients have had at least one cancer (10% of whom risk having had more than one primary cancer, which is quite characteristic of Bloom's); mean age at first cancer onset: 25 yrs (range: 2-49 yrs) acute leukaemias (ALL and ANLL) in 15 % of cases; lymphomas in 15 % as well; these occur mainly before the thirties carcinomas (of a wide variety) occur in 30 % of cases, mainly after the age of 20 yrs benign tumours (10%) Evolution major medical complications apart from cancers are : chronic lung disease, and diabetes mellitus (in 10 %) Prognosis 1/3 of patients are dead at mean age 24 yrs (oldest died at 49 yrs, youngest died before 1 yr) and the mean age of the 2/3 remaining alive patients is 22 yrs (range: 4-46 yrs) Cytogenetics Inborn chromatid/chromosome breaks; triradial and quadriradial figures, in conditions particular symetrical quadriradial configuration involving homologous chromosomes (Class I qr), which are pathognomonic and which may be due to a mitotic crossing-over; micronuclei . diagnosis is on the (pathognomonic) highly elevated spontaneous sister chromatid exchange rate (90 SCE per cell; more than 10 times what is normally found); in some persons a minor population of low SCE cells exists, suggesting a recombination event between maternal and paternal alleles (with different mutations), giving rise to a wild type functional gene; this allowed to localize the gene in a very elegant strategy. heterozygotes are not detectable by cytogenetic studies.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 220 -

sister chromatid exchange in a normal subject (left) and in a Bloom syndrome patient (right) (from: Mounira Amor-Guéret)

Other findings Note slowing of the cell cycle (lenthening of the G1 and S phases) spontaneous mutation rate 10 times higher than normal cells Genes involved and Proteins Complementation no complementation group groups

Gene Name BLM Location 15q26.1 Protein Description 1417 amino acids; contains one ATP binding site, one DEAH box, and two putative nuclear localization signals Expression accumulates to high levels in S phase of the cell cycle, persists in G2/M and sharply declines in G1; hyperphoshorylated in mitosis Localisation nuclear (PML nuclear bodies and nucleolus) Function 3-5 DNA helicase; probable role in DNA replication and double-strand break repair

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 221 - Preferred substrates: G-quadruplex DNA, D-loops structures and X- junctions. Recombinant protein promotes ATP-dependent branch migration of Hollyday junctions. participates in a supercomplex of BRCA1-associated proteins named BASC (BRCA1-Associated genome Surveillance Complex) and in a complex named BRAFT (BLM, RPA, FA, Topoisomerase IIIalpha) containing five of the Fanconia Anemia (FA) complementation group proteins (FANCA, FANCG, FANCC, FANCE and FANCF). Interacts physically and/or functionally with p53, 53BP1,WRN, MLH1, RAD51, TRF2, ligase IV, FEN1 Associated with telomeres and ribosomal DNA repeats. Phosphorylated in mitotic cells through the cdc2 pathway, and in response to DNA damaging agents. Homology with the RecQ helicases Mutations Germinal five BLM mutations introducing amino acid substitutions and four BLM mutations introducing premature nonsense codons into the coding sequence have been described to date; one BLM mutation consisting in a 6 bp deletion accompanied by a 7 bp insertion at nucleic acid position 2281 is common in patients from Ashkenazi Jewish ancestry, leading to a truncated protein of 739 amino acids in length; two BLM mutations, 631delCAA and 1610insA were detected in japanese patients.

External links GeneCards BLM GDB BLM OMIM 210900 Orphanet Bloom syndrome HGMD 135698 Bibliography Bloom's syndrome. I. Genetical and clinical observations in the first twenty seven patients. German J. Am J Hum Genet 1969; 2: 196-227.

Syndromes of the head and neck. Gorlin RJ, Cohen MM, Levin LS. Oxford Monogr Med Genet 1990; 19: 297-300.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 222 - The Bloom's syndome gene product is homologous to RecQ helicases. Ellis NA, Groden J, Ye TZ, Straughen J, Lennon DJ, Ciocci S, Proytcheva M, German J. Cell 1995; 83: 655-666. Medline 96069866 Molecular genetics of Bloom's syndrome. Ellis NA and German J. Hum Mol Genet 1996; 5 Spec No: 1457-1463 (REVIEW). Medline 97029240

Characterization of a new BLM mutation associated with a topoisomerase II alpha defect in a patient with Bloom's syndrom Foucault F, Vaury C, Barakat A, Thibout D, Planchon P, Jaulin C, Praz F, Amor-Gueret M. Hum Mol Genet 1997; 6: 1427-1434. Medline 97449163

Bloom's syndrome. XX. The first 100 cancers. German J Cancer Genet Cytogenet 1997; 93: 100-106. (REVIEW). Medline 9062585

BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal. Kaneko H, Orii KO, Matsui E, Shimozawa N, Fukao T, Matsumoto T, Shimamoto A, Furuichi Y, Hayakawa S, Kasahara K, Kondo N Biochem Biophys Res Commun 1997; 240: 348-353. Medline 98049834

The Bloom's syndrome gene product is a 3'-5' DNA helicase. Karow JK, Chakraverty RK, Hickson ID. J Biol Chem 1997; 272: 30611-30614. Medline 98049515

The Bloom's syndrome helicase unwinds G4 DNA. Sun H, Karow JK, Hickson ID, Maizels N. J Biol Chem 1998; 273: 27587-27592 Medline 9765292

PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1. Ishov AM, Sotnikov AG, Negorev D, Vladimirova OV, Neff N, Kamitani T, Yeh ET, Strauss JF 3rd, Maul GG. J Cell Biol 1999; 147: 221-234.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 223 - Medline 10525530

ATM-dependent phosphorylation and accumulation of endogenous BLM protein in response to ionizing radiation. Ababou M, Dutertre S, Lecluse Y, Onclercq R, Chatton B, Amor-Gueret M. Oncogene 2000; 19: 5955-5963. Medline 11146546

Identification of a novel BLM missense mutation (2706T>C) in a moroccan patient with Bloom's syndrome. Barakat A, Ababou M, Onclercq R, Dutertre S, Chadli E, Hda N, Benslimane A, Amor- Gueret M. Hum Mutat 2000; 6: 584-585. Medline 20321320

Cell cycle regulation of the endogenous wild type Bloom's syndrome DNA helicase. Dutertre S, Ababou M, Onclercq R, Delic J, Chatton B, Jaulin C, Amor-Gueret M. Oncogene 2000; 19: 2731-2738. Medline 20309931

The Bloom's syndrome gene product promotes branch migration of holliday junctions. Karow JK, Constantinou A, Li JL, West SC, Hickson ID. Proc Natl Acad Sci U S A 2000; 97: 6504-6508. Medline 20300930

Binding and melting of D-loops by the Bloom syndrome helicase. van Brabant AJ, Ye T, Sanz M, German III JL, Ellis NA, Holloman WK. Biochemistry 2000; 39: 14617-14625 Medline 11087418

BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J. Genes Dev 2000; 14: 927-939. Medline 20245492

Nuclear structure in normal and Bloom syndrome cells. Yankiwski V, Marciniak RA, Guarente L, Neff NF. Proc Natl Acad Sci U S A 2000; 97: 5214-5219. Medline 10779560

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 224 - Regulation and localization of the Bloom syndrome protein in response to DNA damage. Bischof O, Kim SH, Irving J, Beresten S, Ellis NA, Campisi J. J Cell Biol 2001; 153: 367-380. Medline 11309417

The Bloom syndrome protein interacts and cooperates with p53 in regulation of transcription and cell growth control. Garkavtsev IV, Kley N, Grigorian IA, Gudkov AV. Oncogene 2001; 20: 8276-828 Medline 11781842

The Bloom's syndrome protein (BLM) interacts with MLH1 but is not required for DNA mismatch repair. Langland G, Kordich J, Creaney J, Goss KH, Lillard-Wetherell K, Bebenek K, Kunkel TA, Groden J. J Biol Chem 2001; 276: 30031-30035. Medline 11325959

The Bloom's and Werner's syndrome proteins are DNA structure-specific helicases. Mohaghegh P, Karow JK, Brosh Jr RM Jr, Bohr VA, Hickson ID. Nucleic Acids Res 2001; 29: 2843-2849. Medline 11433031

Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1. Pedrazzi G, Perrera C, Blaser H, Kuster P, Marra G, Davies SL, Ryu GH, Freire R, Hickson ID, Jiricny J, Stagljar I. Nucleic Acids Res 2001; 29: 4378-4386. Medline 11691925

Functional interaction of p53 and BLM DNA helicase in apoptosis. Wang XW, Tseng A, Ellis NA, Spillare EA, Linke SP, Robles AI, Seker H, Yang Q, Hu P, Beresten S, Bemmels NA, Garfield S, Harris CC. J Biol Chem 2001; 276: 32948-32955. Medline 11399766

Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51. Wu L, Davies SL, Levitt NC, Hickson ID. J Biol Chem 2001; 276: 19375-19381. Medline 11278509

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 225 -

Bloom's syndrome protein response to ultraviolet-C radiation and hydroxyurea- mediated DNA synthesis inhibition. Ababou M, Dumaire V, Lecluse Y, Amor-Gueret M. Oncogene 2002; 21: 2079-2088. Medline 11960380

Increased error-prone non homologous DNA end-joining--a proposed mechanism of chromosomal instability in Bloom's syndrome. Gaymes TJ, North PS, Brady N, Hickson ID, Mufti GJ, Rassool FV. Oncogene 2002; 21: 2525-2533 Medline 11971187

The BLM helicase is necessary for normal DNA double-strand break repair. Langland G, Elliott J, Li Y, Creaney J, Dixon K, Groden J. Cancer Res 2002; 62: 2766-2770. Medline 12019152

Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases. Opresko PL, von Kobbe C, Laine JP, Harrigan J, Hickson ID, Bohr VA. J Biol Chem 2002; 277: 41110-41119. Medline 12181313

The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis. Stavropoulos DJ, Bradshaw PS, Li X, Pasic I, Truong K, Ikura M, Ungrin M, Meyn MS. Hum Mol Genet 2002; 11: 3135-3144. Medline 12444098

Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins. von Kobbe C, Karmakar P, Dawut L, Opresko P, Zeng X, Brosh RM Jr, Hickson ID, Bohr VA. J Biol Chem 2002; 277: 22035-22044. Medline 11919194

The processing of Holliday junctions by BLM and WRN helicases is regulated by p53. Yang Q, Zhang R, Wang XW, Spillare EA, Linke SP, Subramanian D, Griffith JD, Li JL, Hickson ID, Shen JC, Loeb LA, Mazur SJ, Appella E, Brosh RM Jr, Karmakar P, Bohr VA, Harris CC. J Biol Chem 2002; 277: 31980-31987.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 226 - Medline 12080066

A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrom Meetei AR, Sechi S, Wallisch M, Yang D, Young MK, Joenje H, Hoatlin ME, Wang W. Mol Cell Biol 2003; 23: 3417-2346. Medline 12724401

Possible anti-recombinogenic role of Bloom's syndrome helicase in double-strand break processing. Onclercq-Delic R, Calsou P, Delteil C, Salles B, Papadopoulo D, Amor-Gueret M. Nucleic Acids Res 2003; 31: 6272-6782. Medline 14576316

BLM helicase-dependent transport of p53 to sites of stalled DNA replication forks modulates homologous recombination. Sengupta S, Linke SP, Pedeux R, Yang Q, Farnsworth J, Garfield SH, Valerie K, Shay JW, Ellis NA, Wasylyk B, Harris CC. EMBO J 2003; 22: 1210-1222. Medline 12606585

Telomere and ribosomal DNA repeats are chromosomal targets of the bloom syndrome DNA helicase. Schawalder J, Paric E, Neff NF. BMC Cell Biol 2003; 4: 15 Medline 14577841

Relatively common mutations of the Bloom syndrome gene in the Japanese population. Kaneko H, Isogai K, Fukao T, Matsui E, Kasahara K, Yachie A, Seki H, Koizumi S, Arai M, Utunomiya J, Miki Y, Kondo N. Int J Mol Med 2004; 14: 439-442. Medline 15289897

A major role for mitotic CDC2 kinase inactivation in the establishment of the mitotic DNA damage checkpoint. Bayart E, Grigorieva O, Leibovitch S, Onclercq-Delic R, Amor-Gueret M. Cancer Res 2004; 64: 8954-8959. Medline 15604258

Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. Sengupta S, Robles AI, Linke SP, Sinogeeva NI, Zhang R, Pedeux R, Ward IM, Celeste A, Nussenzweig A, Chen J, Halazonetis TD, Harris CC.

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 227 - J Cell Biol 2004; 166: 801-813. Medline 15364958

Genetic interactions between BLM and DNA ligase IV in human cell So S, Adachi N, Lieber MR, Koyama H. J Biol Chem 2004; 279: 55433-55442. Medline 15509577

Human bloom protein stimulates flap endonuclease 1 activity by resolving DNA secondary structure. Wang W, Bambara RA. J Biol Chem. 2005; 280: 5391-5399 Medline 15579905 REVIEW articles automatic search in PubMed Last year automatic search in PubMed publications Contributor(s) Written 02-1998 Jean-Loup Huret Updated 09-2000 Mounira Amor-Guéret Updated 02-2005 Mounira Amor-Guéret Citation This paper should be referenced as such : Huret JL . Bloom syndrome. Atlas Genet Cytogenet Oncol Haematol. February 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Tumors/BLO10002.html Amor-Guéret M . Bloom syndrome. Atlas Genet Cytogenet Oncol Haematol. September 2000 . URL : http://www.infobiogen.fr/services/chromcancer/Tumors/BLO10002.html Amor-Guéret M . Bloom syndrome. Atlas Genet Cytogenet Oncol Haematol. February 2005 . URL : http://www.infobiogen.fr/services/chromcancer/Tumors/BLO10002.html © Atlas of Genetics and Cytogenetics in Oncology and Haematology

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 228 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

Dubowitz syndrome

Identity Note Dubowitz syndrome may be confused with Bloom syndrome; another differential diagnosis is fetal alcohol syndrome Inheritance autosomal recessive; heterogeneity cannot be excluded; less than 150 cases described Clinics Note phenotypic spectrum variable Phenotype growth: from normal to severe retardation; intrauterine growth and clinics retardation is frequent; birth weight: 2.3 kg; length: 45 cm; cranial perimeter: 30 cm; delayed bone age. head: microcephaly; high forehead; sparse hair; broad nose; epicanthus; hypertelorism; blepharophimosis; microretrognathia. skin: eczema, a classical sign, may be absent. congenital heart defects in 10%; other malformations: ocular, dental, skeletal, urogenital in male patients; frequent infections. mental retardation in 30-70 % of cases (from normal in 30% to severe retardation in 10%); siezures in 10%high-pitched voice; behaviour problems in 40%; most patients are 'hyperactive, shy, like music'. Neoplastic haematological malignancies and pancytopenia in 10%, childhood risk myelodysplasia in particular; lymphomas Cytogenetics Inborn appears to be normal or near to normal in most cases, although an conditions increased rate of chromosomal breakage has also been descibed External links OMIM 223370 Orphanet Dubowitz syndrome Association Dubowitz syndrome

Bibliography

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 229 - Dubowitz syndrome: review of 141 cases including 36 previously unreported patients. Tsukahara M, Opitz JM Am J Med Genet 1996 May 3;63(1):277-289 Medline 96298286

Syndromes of the head and neck. Gorlin RJ, Cohen MM, Levin LS. Oxford Monogr Med Genet 1990; 19: 304-306.

REVIEW articles automatic search in PubMed Last year automatic search in PubMed publications Contributor(s) Written 02-1998 Jean-Loup Huret and Claude Léonard Citation This paper should be referenced as such : Huret JL and Léonard C . Dubowitz syndrome. Atlas Genet Cytogenet Oncol Haematol. February 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Tumors/DUB10016.html

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 230 - Atlas of Genetics and Cytogenetics in Oncology and Haematology

Fanconi anaemia (updated: old version not available)

Identity Note Fanconi anaemia is a chromosome instability syndrome with progressive bone marrow failure and an increased risk of cancers Other Fanconi pancytopenia names Inheritance autosomal recessive; frequency is about 2.5/105 newborns

Clinics Phenotype growth retardation (70% of cases) and clinics skin abnormalities: hyperpigmentation and/or café au lait spots in 80% squeletal malformations (60%), particularly radius axis defects (absent or hypoplastic thumb or radius...) no immune deficiency (in contrast with most other chromosome instability syndromes) progressive bone marrow failure; mean age of onset of anemia: 8 yrs; diagnosis made before onset of haematologic manifestations in only 30% other: renal anomalies, hypogonadism, mental impairment, heart defects, and perhaps diabetes mellitus, also occur in 10 to 30% of cases Neoplastic myelodysplasia (MDS) and acute non lyphocytic leukaemia (ANLL): risk 15% of cases; i.e. a 15000 fold increased risk of MDS and ANLL has been evaluated in FA, and it has been assumed that 'it is reasonable to regard the Fanconi anemia genotype as "preleukemia"'; mean age at diagnosis: 13-15 yrs hepatocarcinoma (androgen-therapy induced) in 10%; mean age at diagnosis: 16 yrs other cancers in 2-5%: in particular squamous cell carcinoma Treatment androgens and steroids to improve haematopoietic functions; bone marrow transplantation prevents from terminal pancytopenia, and from ANLL as well Prognosis mean age at death: 16 years; most patients die from marrow aplasia (haemorrhage, sepsis), and others from malignancies; MDS and ANLL in

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 231 - FA bear a very poor prognosis (median survival of about 6 mths); survival is also poor in the case of a squamous cell carcinoma. It has recently been shown that significant phenotypic differences were found between the various complementation groups (see below). In FA group A, patients homozygous for null mutations had an earlier onset of anemia and a higher incidence of leukemia than those with mutations producing an altered protein. FA group G patients had more severe cytopenia and a higher incidence of leukemia. FA group C patients had less somatic abnormalities, which, in reverse, were more frequent in the rare groups FA-D, FA-E, and FA-F. FA group G patients patients and patients homozygous for null mutations in FANCA are high-risk groups with a poor hematologic outcome and should be considered as candidates both for frequent monitoring and early therapeutic intervention. There may also be a certain degree of clinical heterogeneity.according to the degree of mosaicism. Therefore, clinical manifestations may be variable within a given family, according to the stage of embryonic development at which the somatic reverse mutation occurred.

Cytogenetics Inborn spontaneous chromatid/chromosome breaks, triradials, quadriradials conditions hypersensitivity to the clastogenic effect of DNA cross-linking agents (increased rate of breaks and radial figures); diepoxybutane, mitomycin C, or mechlorethamine hydrochlorid are used for diagnosis

A: gaps; B: breaks; C: deletion; D: triradials; E: quadriradials; F: complex figures; G: dicentric. Giemsa staining - Editor

Cytogenetics various clonal anomalies are found in MDS or ANLL in Fanconi anaemia of cancer patients, such as the classical -5/del(5q), and -7/del(7q), found in 10 % of

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 232 - cases; telomeres appear to be non randomly involved in FA's clonal anomalies.

Other findings Note slowing of the cell cycle (G2/M transition, with accumulating of cells in G2) impaired oxygen metabolism defective P53 induction

Genes involved and Proteins Note There are 7 complementation groups (A to G). The most prevalent complementation groups are: group A (65-70% of cases), groups C and G (10-15% each) Rare complementation groups are groups B, D, E, and F (<1 to 3 % each). Six genes have been discovered, corresponding to the frequent phenotypes: FANCA in 16q24, FANCC in 9q22, and FANCG in 9p13, and to the rarer phenotypes: FANCD2 in 3p25. FANCE in 6p21, and in 11p15, NOTE The genes FANCB and FANCD1 have yet to be uncovered.

To be noted Clinical diagnosis may, in certain cases, be very difficult; cytogenetic ascertainment is then particularly useful; however, cytogenetic diagnosis may also, at times, be very uncertain; this is a great problem when bone marrow engraftment has been decided in a pancytopenic patient: if this patient has FA, bone marrow conditioning must be very mild, as FA cells are very clastogen sensitive. The recent discover of genes involved in the disease should improve diagnostic ascertainment. FA patients (i.e. patients with defective alleles) may have, in a percentage of cells, a somatic reversion (by revert mutation towards wild- type gene); such a phenomenon is also known in Bloom syndrome, another chromosome instability syndrome

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 233 - External links OMIM 600901 Orphanet Fanconi anemia HGMD 701221 Association http://rio.com/~fafund/FAHTML/FAHome/ Association Association Francaise de la Maladie de Fanconi Registry International Fanconi Anemia Registry (IFAR)

Bibliography Spectrum of anomalies in Fanconi anaemia. Glanz A, Fraser FC J Med Genet 1982; 19(6): 412-416 Medline 83111828

Karyotype evolution in the bone marrow of a patient with Fanconi anemia: breakpoints in clonal anomalies of this disease. Huret JL, Tanzer J, Guilhot F, Frocrain-Herchkovitch C, Savage JR Cytogenet Cell Genet 1988; 48(4): 224-227 Medline 89250662

Leukemia and preleukemia in Fanconi anemia patients. A review of the literature and repAuerbach AD, Allen RGort of the International Fanconi Anemia Registry. Auerbach AD, Allen RG. Cancer Genet Cytogenet 1991; 51(1): 1-12 Medline 91084771

Evidence for at least four Fanconi anaemia genes including FACC on chromosome 9. Strathdee CA, Duncan AM, Buchwald M Nat Genet 1992; 1(3): 196-198 Medline 93265102

Cloning of cDNAs for Fanconi's anaemia by functional complementation. Strathdee CA, Gavish H, Shannon WR, Buchwald M Nature 1992; 356(6372): 763-767 Medline 92244337

Hematologic abnormalities in Fanconi anemia: an International Fanconi Anemia Registry study. Butturini A, Gale RP, Verlander PC, Adler-Brecher B, Gillio AP, Auerbach AD

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 234 - Blood 1994; 84(5): 1650-1655 Medline 94348092

Identification and chromosomal localization of a DNA fragment implicated in the partial correction of the Fanconi anemia group D cellular defect. Diatloff-Zito C, Duchaud E, Viegas-Pequignot E, Fraser D, Moustacchi E Mutat Res 1994; 307(1): 33-42 Medline 94232242

Expression cloning of a cDNA for the major Fanconi anaemia gene, FAA. Lo Ten Foe JR, Rooimans MA, Bosnoyan-Collins L, Alon N, Wijker M, Parker L, Lightfoot J, Carreau M, Callen DF, Savoia A, Cheng NC, van Berkel CG, Strunk MH, Gille JJ, Pals G, Kruyt FA, Pronk JC, Arwert F, Buchwald M, Joenje H Nat Genet; 14(3): 320-323 Medline 97051928

Positional cloning of the Fanconi anaemia group A gene. The Fanconi anaemia/breast cancer consortium. no authors listed Nat Genet 1996; 14(3): 324-328 Medline 97051929

Molecular biology of Fanconi anemia: implications for diagnosis and therapy. D'Andrea AD, Grompe M Blood 1997; 90(5): 1725-1736 Medline 97436532

Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex. Garcia-Higuera I, Kuang Y, Naf D, Wasik J, D'Andrea AD. Mol Cell Biol 1999; 19(7): 4866-4873 Medline 10373536

Association of complementation group and mutation type with clinical outcome in fanconi anemia. European Fanconi Anemia Research Group. Faivre L, Guardiola P, Lewis C, Dokal I, Ebell W, Zatterale A, Altay C, Poole J, Stones D, Kwee ML, van Weel-Sipman M, Havenga C, Morgan N, de Winter J, Digweed M, Savoia A, Pronk J, de Ravel T, Jansen S, Joenje H, Gluckman E, Mathew CG. Blood 2000; 96(13): 4064-4070 Medline 11110674

Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, Grompe M,

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 235 - D'Andrea AD. Mol Cell 2001; 7(2): 249-262 Medline 11239454

Fanconi anemia and DNA repair. Grompe M, D'Andrea A. Hum Mol Genet 2001; 10(20): 2253-2259 Medline 11673408

Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway. Medhurst AL, Huber PA, Waisfisz Q, de Winter JP, Mathew CG. Hum Mol Genet 2001; 10(4): 423-429 Medline 11157805

Fanconi anemia proteins localize to chromatin and the nuclear matrix in a DNA damage- and cell cycle-regulated manner. Qiao F, Moss A, Kupfer GM. J Biol Chem 2001; 276(26): 23391-23396 Medline 11297559

Current knowledge on the pathophysiology of Fanconi anemia: from genes to phenotypes. Yamashita T, Nakahata T. Int J Hematol 2001; 74(1): 33-41 Medline 11530803

Breaks at telomeres and TRF2-independent end fusions in Fanconi anemia. Callen E, Samper E, Ramirez MJ, Creus A, Ortega JJ, Olive T, Badell I, Blasco MA, Surralles J. Hum Mol Genet 2002; 11(4): 439-444. Medline 11854176

REVIEW articles automatic search in PubMed Last year automatic search in PubMed publications

Contributor(s) Written 02-1998 Jean-Loup Huret Updated 06-2002 Jean-Loup Huret

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 236 - Citation This paper should be referenced as such : Huret JL . Fanconi anaemia. Atlas Genet Cytogenet Oncol Haematol. February 1998 . URL : http://www.infobiogen.fr/services/chromcancer/Tumors/FA10001.html Huret JL . Fanconi anaemia. Atlas Genet Cytogenet Oncol Haematol. June 2002 . URL : http://www.infobiogen.fr/services/chromcancer/Tumors/FA10001.html

Atlas Genet Cytogenet Oncol Haematol 1998; 2 (2) - 237 -