Platelet-Derived Growth Factor Receptor, Beta

Atlas of Genetics and Cytogenetics

in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS

Gene Section Mini Review

PDGFRB (platelet-derived growth factor receptor, beta polypeptide) José Luis Vizmanos Departamento de Genética, Facultad de Ciencias, Universidad de Navarra, Pamplona, Spain (JLV)

Published in Atlas Database: July 2005 Online updated version: http://AtlasGeneticsOncology.org/Genes/PDGFRBID21ch5q32.html DOI: 10.4267/2042/38242 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2005 Atlas of Genetics and Cytogenetics in Oncology and Haematology

Identity DNA/RNA Other names: BC032224; J03278: M21616; JTK12; Description PDGFR; CD140B; PDGFR1; PDGF-R-beta 23 exons spanning 149.5 Mb on 5q31-q32. HGNC (Hugo): PDGFRB Transcription is from telomere to centromere. Location: 5q31-q32 Transcription Local order: MXI1 (MAX-interacting protein 1) is 1 transcript in RefSeq encoding NP_002600. 1 more telomeric. XPNPEP1 (X-prolylaminopeptidase 1) transcript in EnsEMBL encoding ENSP00000261799. is more telomeric. Protein Note PDGFRB; Beta platelet-derived growth factor receptor [Precursor]. Description Beta platelet-derived growth factor receptor precursor Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular (PDGF-R-beta) (CD140b antigen). Cytogenetics.

Genomic structure of PDGFRB. Black boxes indicate exons, small ones indicate untranslated exons.

Schematic representation of PDGFRB. Ig-like domains: extracellular immunoglobulin-like domains involved in protein-ligand interaction, TM: transmembrane domain, Split-TK domain: RTK class III cytoplasmic kinase domain with an insertion of 70 to 100 hydrophilic residues.

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Localisation Hybrid/Mutated gene Type I membrane protein. 5' PDE4DIP-PDGFRB 3'. Abnormal protein Function PDE4DIP-PDGFRB. Is receptor that binds specifically to PDGFB and has a tyrosine-protein kinase activity. Is a cell surface t(1;3;5)(p36;p21;q33) tyrosine kinase receptor for members of the platelet- Note derived growth factor family (PDGF). The PDGFRB fusion partner unpublished. Translocation PDGFR/PDGF system includes two receptors described in a patient with a chronic myeloproliferative (PDGFRA and PDGFRB) and four ligands (PDGFRA, disorder. B, C and D). The receptors PDGFRA and PDGFRB are Disease related in sequence and both are members of the class CMPD. III subtype of receptor tyrosine kinases (RTKs). Other class III RTKs are CSF1R, KIT and FLT3. Mature Cytogenetics PDGFRB consist of 1067 amino acids and can bind t(1;3;5)(p36;p21;q33). strongly to PDGF-BB and -DD homodimers, but Hybrid/Mutated gene weakly to AB heterodimers and not to PDGF-AA Unidentified. homodimer. The different ligands seem to induce Abnormal protein different signals. Unidentified. Homology t(2;12;5)(q37;q22;q33) PDGFRB presents homology in several species. It also belongs to GROWTH FACTOR RECEPTOR Note PRECURSOR EC_2.7.1.112 TYROSINE KINASE PDGFRB fusion partner unpublished. protein family. Disease Translocation described in a patient with a Mutations myelodysplastic syndrome. Germinal Cytogenetics t(2;12;5)(q37;q22;q33). See SNPs at EnsEMBL (http://www.ensembl.org/Homo_sapiens/genesnpview? Hybrid/Mutated gene db=coregene=ENSG00000113721). Unidentified. Abnormal protein Implicated in Unidentified. Note t(3;5)(p21;q31) Some rare gene fusions involving PDGFRB have been Note described in several patients with chronic PDGFRB fusion partner unpublished. myeloproliferative disorders (CMPD), myelodysplastic/myeloproliferative syndromes Disease (MDS/MPD) and AML, often associated with Translocation described in a patient with an atypical eosinophilia and splenomegaly. Transformation to CML. acute leukemia has been observed in a minor Cytogenetics proportion of cases. Some of them respond to imatinib t(3;5)(p21;q31). mesylate. Hybrid/Mutated gene t(1;5)(q23;q33) Unidentified. Disease Abnormal protein Described in an 11 month old girl with Unidentified. myelodysplastic/myeloproliferative syndrome with eosinophilia. t(5;7)(q33;q11.2) Prognosis Disease Bad. Described in two patients with CMML/eosinophilia and CMML. Cytogenetics t(1;5)(q23;q33). Prognosis Unknown.

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PDGFRB (platelet-derived growth factor receptor, beta polypeptide) Vizmanos JL

Cytogenetics Prognosis t(5;7)(q33;q11.2). Good, imatinib mesylate responsive disease. Hybrid/Mutated gene Cytogenetics 5' HIP1-PDGFRB 3' t(5;14)(q33;q24). Abnormal protein Hybrid/Mutated gene HIP1-PDGFRB 5' NIN-PDGFRB 3'. t(5;10)(q33;q22) Abnormal protein Disease NIN-PDGFRB. Described in five cases with atypical CML. t(5;14)(q31;q32) Prognosis Disease good, imatinib mesylate responsive disease. Described in a patient with a chronic Cytogenetics myeloproliferative disorder with peripheral blood t(5;10)(q33;q22). monocitosis. Hybrid/Mutated gene Prognosis 5' H4-PDGFRB 3'. Good, imatinib mesylate responsive disease. Abnormal protein Cytogenetics H4-PDGFRB. t(5;14)(q31;q32). t(5;12)(q33;p13) Hybrid/Mutated gene 5' KIAA1509-PDGFRB 3'. Disease Abnormal protein Associated to atypical CML, AML, chronic 5' KIAA1509-PDGFRB 3'. myelomonocytic leukaemia (CMML), chronic eosinophilic leukaemia (CEL) or unclassified t(5;15)(q33;q22) myeloproliferative disorders. Disease Prognosis Described in a patient with a chronic Good. myeloproliferative disorder with eosinophilia. Cytogenetics Prognosis t(5;12)(q33;p13). Imatinib mesylate responsive disease but the patient Hybrid/Mutated gene described resistance was developed. 5' ETV6-PDGFRB 3'. Cytogenetics Abnormal protein t(5;15)(q33;q22). ETV6-PDGFRB. Hybrid/Mutated gene t(5;14)(q33;q32) 5' TP53BP1-PDGFRB 3'. Abnormal protein Disease TP53BP1-PDGFRB. Described in a patient with AML and a t(7;11)(p15;p15) at initial diagnosis, who relapsed with t(5;17)(q33;p11.2) a prominent eosinophilia, hepatosplenomegaly and Disease t(5;14) as an additional cytogenetic abnormality. JMML/CMML. Prognosis Prognosis Good. Good. Cytogenetics Cytogenetics t(5;14)(q33;q32). t(5;17)(q33;p11.2). Hybrid/Mutated gene Hybrid/Mutated gene 5' TRIP11-PDGFRB 3'. 5' HCMOGT-PDGFRB 3' fusion described in an 18 Abnormal protein month old boy with juvenile myelomonocytic leukemia TRIP11-PDGFRB. and eosinophilia. t(5;14)(q33;q24) Abnormal protein Disease HCMOGT-PDGFRB. Described in a patient with a chronic t(5;17)(q33;p13) myeloproliferative disorder with eosinophilia.

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PDGFRB (platelet-derived growth factor receptor, beta polypeptide) Vizmanos JL

Disease Cytogenetics Described in a patient with chronic myelomonocitic t(5;17)(q33;p13). leukemia. Hybrid/Mutated gene Prognosis 5' RABEP1-PDGFRB 3'. Unknown. Abnormal protein RABEP1-PDGFRB.

Breakpoints 17p13 (RABEP1) 1q22 ( PDE4PIP) 17p11 (HCMOGT1)

15q22 (TP53BP1 ) 1q33

5q32 (PDGFRB) 3p21 14q32 (KIAA1509 )

7q11 (HIP1) 14q31 (TRIP11)

10q21 (CCDC6) 14q24 (NIN) 12p13 (ETV6)

PDGFRB and partners- recurrent translocations. Editor 08/2004; last update 11/2004 References Golub TR, Barker GF, Lovett M, Gilliland DG. Fusion of PDGF H4(D10S170), a gene frequently rearranged in papillary thyroid receptor beta to a novel ets-like gene, tel, in chronic carcinoma, is fused to the platelet-derived growth factor myelomonocytic leukemia with t(5;12) chromosomal receptor beta gene in atypical chronic myeloid leukemia with translocation. Cell. 1994 Apr 22;77(2):307-16 t(5;10)(q33;q22). Blood. 2001 Jun 15;97(12):3910-8 Abe A, Emi N, Tanimoto M, Terasaki H, Marunouchi T, Saito Apperley JF, Gardembas M, Melo JV, Russell-Jones R, Bain H. Fusion of the platelet-derived growth factor receptor beta to BJ, Baxter EJ, Chase A, Chessells JM, Colombat M, Dearden a novel gene CEV14 in acute myelogenous leukemia after CE, Dimitrijevic S, Mahon FX, Marin D, Nikolova Z, Olavarria clonal evolution. Blood. 1997 Dec 1;90(11):4271-7 E, Silberman S, Schultheis B, Cross NC, Goldman JM. Response to imatinib mesylate in patients with chronic Ross TS, Bernard OA, Berger R, Gilliland DG. Fusion of myeloproliferative diseases with rearrangements of the Huntingtin interacting protein 1 to platelet-derived growth factor platelet-derived growth factor receptor beta. N Engl J Med. beta receptor (PDGFbetaR) in chronic myelomonocytic 2002 Aug 15;347(7):481-7 leukemia with t(5;7)(q33;q11.2). Blood. 1998 Jun 15;91(12):4419-26 Steer EJ, Cross NC. Myeloproliferative disorders with translocations of chromosome 5q31-35: role of the platelet- Kulkarni S, Heath C, Parker S, Chase A, Iqbal S, Pocock CF, derived growth factor receptor Beta. Acta Haematol. Kaeda J, Cwynarski K, Goldman JM, Cross NC. Fusion of 2002;107(2):113-22 H4/D10S170 to the platelet-derived growth factor receptor beta in BCR-ABL-negative myeloproliferative disorders with a Baxter EJ, Kulkarni S, Vizmanos JL, Jaju R, Martinelli G, t(5;10)(q33;q21). Cancer Res. 2000 Jul 1;60(13):3592-8 Testoni N, Hughes G, Salamanchuk Z, Calasanz MJ, Lahortiga I, Pocock CF, Dang R, Fidler C, Wainscoat JS, Boultwood J, Magnusson MK, Meade KE, Brown KE, Arthur DC, Krueger Cross NC. Novel translocations that disrupt the platelet-derived LA, Barrett AJ, Dunbar CE. Rabaptin-5 is a novel fusion growth factor receptor beta (PDGFRB) gene in BCR-ABL- partner to platelet-derived growth factor beta receptor in negative chronic myeloproliferative disorders. Br J Haematol. chronic myelomonocytic leukemia. Blood. 2001 Oct 2003 Jan;120(2):251-6 15;98(8):2518-25 Garcia JL, Font de Mora J, Hernandez JM, Queizan JA, Schwaller J, Anastasiadou E, Cain D, Kutok J, Wojiski S, Gutierrez NC, Hernandez JM, San Miguel JF. Imatinib Williams IR, LaStarza R, Crescenzi B, Sternberg DW, mesylate elicits positive clinical response in atypical chronic Andreasson P, Schiavo R, Siena S, Mecucci C, Gilliland DG.

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myeloid leukemia involving the platelet-derived growth factor Morerio C, Acquila M, Rosanda C, Rapella A, Dufour C, receptor beta. Blood. 2003 Oct 1;102(7):2699-700 Locatelli F, Maserati E, Pasquali F, Panarello C. HCMOGT-1 is a novel fusion partner to PDGFRB in juvenile myelomonocytic Gunby RH, Cazzaniga G, Tassi E, Le Coutre P, Pogliani E, leukemia with t(5;17)(q33;p11.2). Cancer Res. 2004 Apr Specchia G, Biondi A, Gambacorti-Passerini C. Sensitivity to 15;64(8):2649-51 imatinib but low frequency of the TEL/PDGFRbeta fusion protein in chronic myelomonocytic leukemia. Haematologica. Vizmanos JL, Novo FJ, Román JP, Baxter EJ, Lahortiga I, 2003 Apr;88(4):408-15 Larráyoz MJ, Odero MD, Giraldo P, Calasanz MJ, Cross NC. NIN, a gene encoding a CEP110-like centrosomal protein, is Wilkinson K, Velloso ER, Lopes LF, Lee C, Aster JC, Shipp fused to PDGFRB in a patient with a t(5;14)(q33;q24) and an MA, Aguiar RC. Cloning of the t(1;5)(q23;q33) in a imatinib-responsive myeloproliferative disorder. Cancer Res. myeloproliferative disorder associated with eosinophilia: 2004 Apr 15;64(8):2673-6 involvement of PDGFRB and response to imatinib. Blood. 2003 Dec 1;102(12):4187-90 Levine RL, Wadleigh M, Sternberg DW, Wlodarska I, Galinsky I, Stone RM, DeAngelo DJ, Gilliland DG, Cools J. KIAA1509 is Grand FH, Burgstaller S, Kühr T, Baxter EJ, Webersinke G, a novel PDGFRB fusion partner in imatinib-responsive Thaler J, Chase AJ, Cross NC. p53-Binding protein 1 is fused myeloproliferative disease associated with a t(5;14)(q33;q32). to the platelet-derived growth factor receptor beta in a patient Leukemia. 2005 Jan;19(1):27-30 with a t(5;15)(q33;q22) and an imatinib-responsive eosinophilic myeloproliferative disorder. Cancer Res. 2004 Oct This article should be referenced as such: 15;64(20):7216-9 Vizmanos JL. PDGFRB (platelet-derived growth factor Jones AV, Cross NC. Oncogenic derivatives of platelet-derived receptor, beta polypeptide). Atlas Genet Cytogenet Oncol growth factor receptors. Cell Mol Life Sci. 2004 Haematol. 2005; 9(4):298-302. Dec;61(23):2912-23

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