DOCSLIB.ORG

MINI-REVIEW Centric and Pericentric Chromosome Rearrangements In

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
MINI-REVIEW Centric and Pericentric Chromosome Rearrangements In Leukemia (1999) 13, 671–678 1999 Stockton Press All rights reserved 0887-6924/99 $12.00 http://www.stockton-press.co.uk/leu MINI-REVIEW Centric and pericentric chromosome rearrangements in hematopoietic malignancies R Berger and M Busson-Le Coniat INSERM U434 and CNRS SD 401 No. 434, Institut de Ge´ne´tique Mole´culaire, Paris, France Cytogenetic and fluorescence in situ hybridization (FISH) lymphoblastic leukemia, have been described as nonrandom analysis of 10 patients with various hematopoietic malig- abnormalities in hematopoietic malignancies.6–10 Other nancies revealed the presence of dicentric chromosomes or pericentric chromosome rearrangements. Dicentrics were only examples of dicentric chromosomes implying various chro- ascertained by FISH studies in six patients. Two types of peri- mosomes occurring as clonal abnormalities, have been centric chromosome rearrangements have been observed: reported to be present in hematopoietic disorders (Table 1). ‘classical’ dicentrics with two clearly separated centromeric Dicentrics may be difficult to detect with banding techniques regions, and more unusual rearrangements with a breakpoint if the two centromeres are very closely located on rearranged within the centromeric or heterochromatic area, but outside the chromosomes. This difficulty can be overcome by use of FISH, alphoid domain. FISH analysis of partial chromosome 1 q dupli- cations present in three Burkitt lymphoma cell lines confirmed and it has been shown that a large number of isochromosomes the partial involvement of the non-alphoid centromeric domain identified by chromosome banding analysis actually are iso- in the duplicated chromosome segment. The incidence of cen- dicentric chromosomes (Table 1). The overall frequency of tromeric and pericentromeric rearrangements in hematopoietic isochromosomes in human malignancies was 9.9% in 18 160 malignancies may be higher than hitherto admitted. The neoplasms11 and unevenly distributed according to the type chromosomal localization of these rearrangements suggests of tumors. several mechanisms possibly involved in the malignant process and deserves more systematic study. The present report underlines the importance of FISH tech- Keywords: hematopoietic malignancies; chromosomes; dicentric; niques to detect dicentric chromosomes and identify pericen- pericentric rearrangements tric rearrangements occurring as clonal abnormalities in malignant blood disorders. This study was initially based upon Introduction Table 1 Dicentric chromosomes in hematopoietic malignancies Dicentric chromosomes classically are instable structures Disease Ref.a prone to be broken at anaphase. While dicentric chromo- somes are rare in normal cells, their frequency is increased Dicentric chromosomes when the cells are exposed to mutagenic agents and ionizing dic(1;15)(p11;p11) MDS, PV 56 radiations. Dicentrics resulting from irradiation from various dic(5;7)(p13;p11) AML 57 sources (X-rays, gamma rays) were also shown to be instable dic(5;17) MDS, CML-BC 58–60 in somatic cells since they disappear throughout successive dic(7;9)(p11–p13;q11) ALL 61,62 mitoses. Dicentric chromosomes, however, have been dic(7;12)(p11;p12) ALL 62 dic(9;12)(p11–13;p11–12) ALL, sAML, 6,7, 63–65 observed in malignant cells as clonal abnormalities with a CML-BC, variable incidence according to the type of tumor examined. ATL, NHL Since such dicentrics persist during cell proliferation, it has dic(9;20)(p11–13;q11) ALL 8–10 been hypothesized that one centromere was functionally inac- dic(12;13)(p11;p13) AML, MDS 66 tive. The abnormal chromosome could consequently escape dic(12;17)(p11;p12) ALL 62 breakage at anaphase. The hypothesis of two kinds of cen- dic(16;22)(q11;p11) MDS, sAML 67 dic(17;18)(p11;p11–12) AML, CML-BC, 68,69 tromeres, active and inactive, was supported by the fact that APL the CENP-C and CENP-E centromere constitutive binding pro- dic(17;22) CML 70 teins are necessary components of functional centromeres but whole arm chromosome various hemato- 18 not of inactive ones.1,2 The centromere is, indeed, a complex translocations poietic disorders structure, associating various DNA subtypes and proteins, dif- ferently associated within the different chromosomes. Alpha Isodicentric chromosomes idic(8)(p11) T-PLL 71 satellite (alphoid) DNA, which is believed to play an idic(12)(q12) MDS, ALL 64, 72 3,4 important role in the function of the centromere, is a family idic(14)(q11) T-CLL, sMDS 73, 74 of satellite DNAs including several subtypes.5 Some idic(17)(p11) AML, CML 75–81 sequences are chromosome-specific, allowing their use as idic(21)(p11) AML 82 markers in techniques of fluorescence in situ hybridization idic(Ph) CML, AML 70, 83 (FISH) to human cells. idic(X)(q13) AML, MDS, MPD 84 Some recurrent dicentric chromosomes, such as dic(9;12)(p11–13;p11–12) and dic(9;20)(p11;q11) in acute ALL, acute lymphoblastic leukemia; AML, acute myeloblastic leuke- mia; sAML, secondary AML; APL, acute promyelocytic leukemia; CML, chronic myeloid leukemia; CML-BC, blastic crisis of CML; MDS, myelodysplastic syndrome; MPD, myeloproliferative disorder; Correspondence: R Berger, U434, 27 rue Juliette Dodu, 75010, Paris, NHL, non-Hodgkin lymphoma; PV, polycythemia vera; T-PLL, T cell France; Fax: 33 1 5372 51 92 prolymphocytic leukemia. Received 7 December 1998; accepted 21 January 1999 aSee also Ref. 17. Mini-review R Berger and M Busson-Le Coniat 672 the finding of aberrant heterochromatin segments in D9Z1) and beta satellite probes (Oncor, D9Z5) specific to rearranged chromosomes, either in possible or obvious dicen- chromosome 9, YACs (from the CEPH library, Paris, France) tric chromosomes, or in translocations mainly involving the 882b3 covering the BCL9 locus,15 978e4 covering the ARNT- long arm of chromosome 1. Ten patients and three cell lines AF1q loci, 742f9 covering the MLL locus, and 936e2 covering with these criteria were chosen for the study. While the inci- the TEL/ETV6 locus, cosmid 19q covering the telomeric part dence of these abnormalities in hematopoietic malignancies of chromosome 19 (L Kearney, MRC Molecular Haematology, cannot be ascertained at the present time, the aim of this John Radcliffe Hospital, Oxford, UK), BAC 16091 and PAC report is to focus on these rearrangements which suggest 16093 corresponding to chromosome bands 7q11–7q21 (G several working hypotheses. Gilliland, Brigham and Women’s Hospital, and Howard Hughes Institute, Philadelphia, USA). Materials and methods Results Patients Analysis of FISH studies of patients (and cell lines) roughly The clinical and hematological data of 10 patients examined confirmed the results of conventional banded karyotype for malignant blood disorders in the Department of Hematol- analysis in most of the cases (Figure 1). However, some abnor- ogy of the Saint-Louis Hospital (Paris) are summarized in malities were found to be better or differently defined with Table 2. In addition three Burkitt lymphoma (BL) cell lines, FISH techniques (Table 3). Dicentric chromosomes or pericen- BL2, BL3, and LY66,12,13 were re-examined with FISH tric rearrangements were present in all patients examined. techniques. Patient 1, therapy-induced AML, M4 after multiple mye- Chromosome studies loma: The karyotype was complex. The chromosome 22 painting probe showed various rearrangements of chromo- Chromosome studies were performed on bone marrow and/or some 22, including add(22)(q13), and del(22)(q11). FISH peripheral blood cells after short-term culture, and on cultures analysis with several probes (chromosome 5, 12, and 22 of BL cell lines. GTG and/or RHG banding techniques were whole chromosome painting, YAC 936e2) showed that the applied and the chromosomes were classified according to the add(22)(q13) chromosome was dicentric, including cen(22) international nomenclature. The results of banded karyotype and cen(8) with insertion of a segment of 12p including the analyses are summarized in Table 3. ETV6/TEL locus (YAC 936e2) between the 22 and 8 fragments. A second marker, add(12)(p12), was also dic, dic(5;12)(q12:p12). Fluorescence in situ hybridization (FISH) FISH techniques14 were applied on metaphase chromosomes Patient 2, ALL: Chromosomes 1 were analyzed with DAPI using various molecular probes depending on the abnormali- staining and a chromosome 1-specific alpha satellite DNA ties studied: whole chromosome painting probes for chromo- probe. A faint heterochromatin-like band was present on the somes 5, 9, 12, 17, 18, 22 (U301 INSERM) and 1 (STAR*FISH long arm of the rearranged chromosome 1, at the limit of its 1066-1B, Cambio, Byosis, Compie`gne, France), 8 (p5201 partial duplication suggesting that the breakpoint was located Coatsome, Oncor, Illkirch, France), alpha satellite probes spe- within band 1q12. Moreover, this band was not labeled with cific to chromosomes 1, 12, 17, and 18 (Oncor, D1Z5, the ‘alphoid’ probe as the normal centromeric regions were. D12Z3, D17Z1, and D18Z1), ‘classical’ satellite (Oncor, This pattern of labeling indicates that the DNA breakpoint Table 2 Clinical and hematological data of 10 patients with hematopoietic malignancies No. CG Sex/Age Diagnosis Bone marrow Peripheral blood Follow-up % blasts Leukocytes Hemoglobin Platelets ×109/l (blasts g/dl ×109/l 1 3462 M/42 y tAML-M4 (MM) 82 35 (36) 8.9 110 — 2 98033 M/3 y ALL-L2 (B) 93 45.6 (84) 9.5 33 CR, 1 m+ 3 2559 F/18 m AML-M4 50 60 (31) 12.9 27 CR, R:7 m, D:8 m 4 97290 M/18 m ALL-L1 (B) 93 47 (83) 8.3 96 CR 5 95276 F/25 y AML-M1 98 159 (94) 9.3 50 CR 6 97220 M/2.5 y AML-M5 79 65 (66) 10.2 280 CR 7 8513 F/2 y ALL (B) 32 4.3 (40) 7.9 50 CR, 6y+ 8 8136 F/8 y ALL-L2 (B) 68 1.3 (0) 7.5 43 CR F/18 y ALL-L2 (R) 89 8.9 (49) 11 6 CR, R:19 m F/19 y ALL-L2 (R2) D: 5 y 4 m 9 4082 F/11 y ALL-L2 (B) 100 7.6 (68) 9.6 46 CR 10 97192 F/62 y AML-M6 21 4.3 (1%) 7.7 89 CR, 6 m+ AML, acute myeloblastic leukemia; tAML, therapy-related, AML; MM, multiple myeloma; ALL, acute lymphoblastic leukemia; M1, M4, M5, M6, L1, L2, FAB subclass; B, B lineage; R, relapse; R2, second relapse; CR, complete remission; D, dead.
Load more

Recommended publications
  • Assignment of the AK1:Np:ABO Linkage Group to Human Chromosome 9 (Somatic Cell Hybrids/Enzyme Markers/Gene Localization) A
    Proc. Nat. Acad. Sci. USA Vol. 73, No. 3, pp. 895-899, March 1976 Genetics Assignment of the AK1:Np:ABO linkage group to human chromosome 9 (somatic cell hybrids/enzyme markers/gene localization) A. WESTERVELD*§, A. P. M. JONGSMA*, P. MEERA KHANt, H. VAN SOMERENt, AND D. BOOTSMA* * Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands; t Department of Human Genetics, State University, Leiden, The Netherlands; and * Medical Biological Laboratory TNO, P.O. Box 45, Rijswijk 2100, The Netherlands Communicated by Victor A. McKusick, January 8,1976 ABSTRACT In man-Chinese hamster somatic cell hy- cytes were obtained from peripheral blood of male and fe- brids the segregation patterns of the loci for 25 human en- male donors. The details on production, isolation, and propa- zyme markers and human chromosomes were studied. The results provide evidence for the localization of the gene for gation of these hybrids have been published elsewhere (11). adenylate kinase-1 (AKI) on chromosome 9. Since the loci for In the hybrid and parental cell populations the following the ABO blood group (ABO), nail-patella syndrome (Np), and enzymes were analyzed by means of Cellogel electrophore- AK1 are known to be linked in man, the ABO.Np:AKj link- sis: glucose-6-phosphate dehydrogenase (G6PD); phospho- age group may be assigned to chromosome 9. glycerate kinase (PGK); a-galactosidase-A (a-Gal A); lactate dehydrogenases (LDH-A, LDH-B); 6-phosphogluconate de- In man several electrophoretically separable isoenzymes for hydrogenase (6PGD); phosphoglucomutases (PGMI, PGMs); adenylate kinase (AK; EC 2.7.4.3) have been described (1).
    [Show full text]
  • Epigenetic Control of Mammalian Centromere Protein Binding: Does DNA Methylation Have a Role?
    Journal of Cell Science 109, 2199-2206 (1996) 2199 Printed in Great Britain © The Company of Biologists Limited 1996 JCS3386 Epigenetic control of mammalian centromere protein binding: does DNA methylation have a role? Arthur R. Mitchell*, Peter Jeppesen, Linda Nicol†, Harris Morrison and David Kipling MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK *Author for correspondence (internet [email protected]) †Present address: MRC Reproductive Biology Unit, Edinburgh, UK SUMMARY Chromosome 1 of the inbred mouse strain DBA/2 has a block of minor satellite DNA sequences on chromosome 1. polymorphism associated with the minor satellite DNA at The binding of the CENP-E protein does not appear to be its centromere. The more terminal block of satellite DNA affected by demethylation of the minor satellite sequences. sequences on this chromosome acts as the centromere as We present a model to explain these observations. This shown by the binding of CREST ACA serum, anti-CENP- model may also indicate the mechanism by which the B and anti-CENP-E polyclonal sera. Demethylation of the CENP-B protein recognises specific sites within the arrays minor satellite DNA sequences accomplished by growing of minor satellite DNA on mouse chromosomes. cells in the presence of the drug 5-aza-2′-deoxycytidine results in a redistribution of the CENP-B protein. This protein now binds to an enlarged area on the more terminal Key words: Centromere satellite DNA, Demethylation, Centromere block and in addition it now binds to the more internal antibody INTRODUCTION A common feature of many mammalian pericentromeric domains is that they contain families of repetitive DNA The centromere of mammalian chromosomes is recognised at sequences (Singer, 1982).
    [Show full text]
  • Chromosomal Assignment of the Genes for Human Aldehyde Dehydrogenase-1 and Aldehyde Dehydrogenase-2 LILY C
    Am J Hum Genet 38:641-648, 1986 Chromosomal Assignment of the Genes for Human Aldehyde Dehydrogenase-1 and Aldehyde Dehydrogenase-2 LILY C. Hsu,', AKIRA YOSHIDA,' AND T. MOHANDAS2 SUMMARY Chromosomal assignment of the genes for two major human aldehyde dehydrogenase isozymes, that is, cytosolic aldehyde dehydrogenase-1 (ALDH1) and mitochondrial aldehyde dehydrogenase-2 (ALDH2) were determined. Genomic DNA, isolated from a panel of mouse- human and Chinese hamster-human hybrid cell lines, was digested by restriction endonucleases and subjected to Southern blot hybridiza- tion using cDNA probes for ALDH1 and for ALDH2. Based on the distribution pattern of ALDH1 and ALDH2 in cell hybrids, ALDHI was assigned to the long arm of human chromosome 9 and ALDH2 to chromosome 12. INTRODUCTION Two major and at least two minor aldehyde dehydrogenase isozymes exist in human and other mammalian livers. One of the major isozymes, designated as ALDH 1, or E1, is of cytosolic origin, and another major isozyme, designated as ALDH2 or E2, is of mitochondrial origin. The two isozymes are different from each other with respect to their kinetic properties, sensitivity to disulfiram inactivation, and protein structure [1-5]. Remarkable racial differences be- tween Caucasians and Orientals have been found in these isozymes. Approxi- mately 50% of Orientals have a variant form of ALDH2 associated with dimin- ished activity, while virtually all Caucasians have the wild-type active ALDH2 Received July 10, 1985; revised September 23, 1985. This work was supported by grant AA05763 from the National Institutes of Health. ' Department of Biochemical Genetics, Beckman Research Institute of the City of Hope, Duarte, CA 91010.
    [Show full text]
  • Extra Euchromatic Band in the Qh Region of Chromosome 9
    J Med Genet: first published as 10.1136/jmg.22.2.156 on 1 April 1985. Downloaded from 156 Short reports two centromeres indicated by two distinct C bands but only I HANCKE AND K MILLER one primary constriction at the proximal C band. The two Department of Human Genetics, C bands were separated by chromosomal material staining Medizinische Hochschule Hannover, pale in G banding and intensely dark in R banding (fig 1). Hannover, Both NORs could be observed in satellite associations (fig Federal Republic of Germany. 2). The chromosome was therefore defined as pseudo- dicentric chromosome 21 (pseudic 21). The same chromo- References some was found in the proband's father and paternal Balicek P, Zizka, J. Intercalar satellites of human acrocentric grandmother. chromosomes as a cytological manifestation of polymorphisms Acrocentric chromosomes with a short arm morphology in GC-rich material? Hum Genet 1980;54:343-7. similar to that presented here have been reported by 2 Ing PS, Smith SD. Cytogenetic studies of a patient with Balicek and Zizka.' These authors paid no attention to the mosaicism of isochromosome 13q and a dicentric (Y;13) activity of the centromeres. The suppression of additional translocation showing differential centromeric activity. Clin centromeres is indicated by the presence of only one Genet 1983;24:194-9. primary constriction as shown by Ing and Smith2 in a 3 Passarge E. Analysis of chromosomes in mitosis and evaluation dicentric (Y;13) transtocation. Variants of acrocentric of cytogenetic data. 5. Variability of the karyotype. In: Schwarzacher HG, Wolf U, eds. Methods in human cytogene- chromosomes are often observed in patients with congen- tics.
    [Show full text]
  • Linear Increase of Structural and Numerical Chromosome 9 Abnormalities in Human Sperm Regarding Age
    European Journal of Human Genetics (2003) 11, 754–759 & 2003 Nature Publishing Group All rights reserved 1018-4813/03 $25.00 www.nature.com/ejhg ARTICLE Linear increase of structural and numerical chromosome 9 abnormalities in human sperm regarding age Merce` Bosch1, Osvaldo Rajmil2, Josep Egozcue3 and Cristina Templado*,1 1Departament de Biologia Cel.lular, Fisiologia i Immunologia, Facultat de Medicina, Universitat Auto`noma de Barcelona, Bellaterra 08193, Spain; 2Servei d’Andrologia, Fundacio´ Puigvert, Barcelona 08025, Spain; 3Departament de Biologia Cel.lular, Fisiologia i Immunologia, Facultat de Cie`ncies, Universitat Auto`noma de Barcelona, Bellaterra 08193, Spain A simultaneous four-colour fluorescence in situ hybridisation (FISH) assay was used in human sperm in order to search for a paternal age effect on: (1) the incidence of structural aberrations and aneuploidy of chromosome 9, and (2) the sex ratio in both normal spermatozoa and spermatozoa with a numerical or structural abnormality of chromosome 9. The sperm samples were collected from 18 healthy donors, aged 24–74 years (mean 48.8 years old). Specific probes for the subtelomeric 9q region (9qter), centromeric regions of chromosomes 6 and 9, and the satellite III region of the Y chromosome were used for FISH analysis. A total of 190 117 sperms were evaluated with a minimum of 10 000 sperm scored from each donor. A significant linear increase in the overall level of duplications and deletions for the centromeric and subtelomeric regions of chromosome 9 (Pr0.002), chromosome 9 disomy (Po0.0001) as well as diploidy (Po0.0001) was detected in relation to age. The percentage of increase for each 10-year period was 29% for chromosome 9 disomy, 18.8% for diploidy, and ranged from 14.6 to 28% for structural aberrations.
    [Show full text]
  • Microcephaly Genes and Risk of Late-Onset Alzheimer Disease
    ORIGINAL ARTICLE Microcephaly Genes and Risk of Late-onset Alzheimer Disease Deniz Erten-Lyons, MD,*w Beth Wilmot, PhD,zy Pavana Anur, BS,z Shannon McWeeney, PhD,zyJ Shawn K. Westaway, PhD,w Lisa Silbert, MD,w Patricia Kramer, PhD,w and Jeffrey Kaye, MD*w Alzheimer’s Disease Neuroimaging Initiative ratio=3.41; confidence interval, 1.77-6.57). However, this associa- Abstract: Brain development in the early stages of life has been tion was not replicated using another case-control sample research suggested to be one of the factors that may influence an individual’s participants from the Alzheimer Disease Neuroimaging Initiative. risk of Alzheimer disease (AD) later in life. Four microcephaly We conclude that the common variations we measured in the 4 genes, which regulate brain development in utero and have been microcephaly genes do not affect the risk of AD or that their effect suggested to play a role in the evolution of the human brain, were size is small. selected as candidate genes that may modulate the risk of AD. We examined the association between single nucleotide polymorphisms Key Words: Alzheimer disease, microcephaly genes, cognitive tagging common sequence variations in these genes and risk of AD reserve in two case-control samples. We found that the G allele of (Alzheimer Dis Assoc Disord 2011;25:276–282) rs2442607 in microcephalin 1 was associated with an increased risk of AD (under an additive genetic model, P=0.01; odds Received for publication June 2, 2010; accepted December 2, 2010. enetics has been suggested to play a role in variations From the *Portland Veterans Affairs Medical Center; wDepartment of Gin cognitive function in late life.1 One way in which Neurology; zOregon Clinical and Translational Research Center; genes may play a role in cognitive function in late life is yDivision of Bioinformatics and Computational Biology, Depart- through providing an “initial endowment” that is more ment of Medical Informatics and Clinical Epidemiology; and JDivision of Biostatistics, Department of Public Health and resistant to age-related changes.
    [Show full text]
  • Numerical Chromosome 1, 7, 9, and 11 Aberrations in Bladder Cancer Detected by in Situ Hybridization1
    [CANCER RESEARCH 51, 644-651, January 15. 1991] Numerical Chromosome 1, 7, 9, and 11 Aberrations in Bladder Cancer Detected by in Situ Hybridization1 Anton H. N. Hopman,2 Olof Moesker, A. Wim G. B. Smeets, Ruud P. E. Pauwels, G. Peter Vooijs, and Frans C. S. Ramaekers Department of Pathology, L'niversity //ospitai Nijmegen, fieert Grooteplein Zulu 24, 6525 (iA, .\ijmegen ¡A.H. N. H., O. .\t., C. P. ('./.' Stickling Ziekenkuisapotkeek en Klinisch Laboratorium l'enray [A. H'. G. B. S.J; Department of Urology, Hospital I enlo-1 'enray [R. P. K. P.], and Department of Molecular Cell Biology, L'nirersity ofLimhurg, Maastricht ¡A.H. N. H., F. C. S. R.], The Netherlands. ABSTRACT studies we demonstrated that this approach enables a routine screening of large tumor cell populations in, for example, Forty transitional cell carcinomas of the human urinary bladder (TCCs) TCCs4 (5, 10). Furthermore, ISH enables the detection of minor were examined for numerical aberrations of chromosomes 1, 7, 9, and 11 by in situ hybridization using chromosome-specific probes. Our inter- cell populations or imbalance in chromosome copy number phase cytogenetic study of 24 low-grade, noninvasive TCCs, which were within one tumor. near-diploid by flow cytometry, showed a numerical aberration for at By means of conventional karyotyping nonrandom chromo least I of these chromosomes in 14 of these cases. Most strikingly, a some aberrations involving chromosomes 1, 7, 9, and 11 have monosomy for chromosome 9 was found in 9 of 24 low-grade TCCs. A been detected in bladder cancer.
    [Show full text]
  • Duplication 9P and Their Implication to Phenotype
    Guilherme et al. BMC Medical Genetics (2014) 15:142 DOI 10.1186/s12881-014-0142-1 RESEARCH ARTICLE Open Access Duplication 9p and their implication to phenotype Roberta Santos Guilherme1, Vera Ayres Meloni1, Ana Beatriz Alvarez Perez1, Ana Luiza Pilla1, Marco Antonio Paula de Ramos1, Anelisa Gollo Dantas1, Sylvia Satomi Takeno1, Leslie Domenici Kulikowski2 and Maria Isabel Melaragno1* Abstract Background: Trisomy 9p is one of the most common partial trisomies found in newborns. We report the clinical features and cytogenomic findings in five patients with different chromosome rearrangements resulting in complete 9p duplication, three of them involving 9p centromere alterations. Methods: The rearrangements in the patients were characterized by G-banding, SNP-array and fluorescent in situ hybridization (FISH) with different probes. Results: Two patients presented de novo dicentric chromosomes: der(9;15)t(9;15)(p11.2;p13) and der(9;21)t(9;21) (p13.1;p13.1). One patient presented two concomitant rearranged chromosomes: a der(12)t(9;12)(q21.13;p13.33) and an psu i(9)(p10) which showed FISH centromeric signal smaller than in the normal chromosome 9. Besides the duplication 9p24.3p13.1, array revealed a 7.3 Mb deletion in 9q13q21.13 in this patient. The break in the psu i(9) (p10) probably occurred in the centromere resulting in a smaller centromere and with part of the 9q translocated to the distal 12p with the deletion 9q occurring during this rearrangement. Two patients, brother and sister, present 9p duplication concomitant to 18p deletion due to an inherited der(18)t(9;18)(p11.2;p11.31)mat.
    [Show full text]
  • Chromosome 9 Deletions and Recurrence of Superficial
    Oncogene (2000) 19, 6317 ± 6323 ã 2000 Nature Publishing Group All rights reserved 0950 ± 9232/00 $15.00 www.nature.com/onc Chromosome 9 deletions and recurrence of super®cial bladder cancer: identi®cation of four regions of prognostic interest Maryse Simoneau1,He leÁ ne LaRue1, Tahar O Aboulkassim1, FrancËois Meyer1, Lynne Moore1 and Yves Fradet*,1 1Centre de recherche en canceÂrologie de l'Universite Laval, Centre Hospitalier Universitaire de QueÂbec, Pavillon L'HoÃtel-Dieu de QueÂbec, QueÂbec, Canada In a previous study, loss of heterozygosity (LOH) of 28 various grades and stages, however, in low stage chromosome 9 microsatellite markers was assessed on tumors, they are often the only genetic anomaly 139 Ta/T1 bladder tumors. LOH at one or more loci identi®ed. In a previous study of chromosome 9 was detected in 67 tumors, 62 presenting subchromoso- LOH on a series of 139 primary Ta, T1 bladder mal deletions. One hundred and thirty-three of these tumors obtained at initial diagnosis (Simoneau et al., patients have now been followed for up to 8 years. The 1999) we found deletion of at least one chromosome 9 purpose of the present study was to evaluate the potential marker in 48% of tumors. Chromosome 9 monosomy biological signi®cance of chromosome 9 deletions in was a rare event and deletions on 9q were twice as super®cial bladder tumors at initial diagnosis. High frequent as deletions on 9p. Moreover, only 4% of grade was associated with LOH (P=0.004). Large cases had deletions on 9p only. This suggests that tumors carried more frequently 9p deletions (P=0.022).
    [Show full text]
  • Chromosomal Rearrangements Genetic Variation Alterationsalterations Inin Chromosomechromosome Structurestructure
    chromosomal rearrangements Genetic variation AlterationsAlterations inin ChromosomeChromosome StructureStructure ! There are two primary ways in which the structure of chromosomes can be altered – 1. The total amount of genetic information in the chromosome can change " Decrease: Deficiencies/Deletions " Increase: Duplications & Insertions – 2. The genetic material may remain the same, but is rearranged " Inversions " Translocations PeCtoerp Jy.r Riguhsts e©llT, ihGee nMetciGcsr: aCwop-Hyriilgl hCt o©m Ppeaanriseosn, IEndcu.c Pateiromn,i sInsico.,n p ruebqliusihriendg faosr B reenpjarmodinu cCtuiomnm oirn gdsisplay 3 Chromosomal aberations/ rearrangements Chromosomal abberations/ rearrangements deletion Duplication Inversion translocation. Chromosomal abberations/ rearrangements • For chromosomal rearrangement to occur, there has to be two or more double-stranded breaks in the chromosomes of a cell. • DSBs are potentially lethal, unless they are repaired by repair enzymes. Chromosomal rearrangements • If the two ends of the same break are rejoined, the original DNA order is restored. • If the ends of two different breaks are joined together, results in a chromosomal rearrangement. • The only chromosomal rearrangements that survive meiosis are those that produce DNA molecules that have one centromere and two telomeres. • acentric chromosome: Without a centromere • Do not get dragged to either pole at anaphase of mitosis or meiosis Chromosomal • Are not incorporated into either progeny nucleus. rearrangements Therefore acentric chromosomes are not inherited. Chromosomal Re-arragements • Dicentric chromosome: With two centromere • pulled simultaneously to opposite poles at anaphase, forming an anaphase bridge. • Generally do not get incorporated into either progeny cell. • A chromosome lacking a telomere, cannot replicate properly Chromosomal • The larger the segment Re-arragements that is lost or duplicated, the more chance, that it will cause phenotypic abnormalities.
    [Show full text]
  • Familial Bone Marrow Monosomy 7 Evidence That the Predisposing Locus Is Not on the Long Arm of Chromosome 7 Kevin M
    Familial Bone Marrow Monosomy 7 Evidence That the Predisposing Locus Is Not on the Long Arm of Chromosome 7 Kevin M. Shannon,* All G. Turhan,*$ Sharon S. Y. Chang,"1 Anne M. Bowcock,' Paul C. J. Rogers,** William L. Carroll,# Morton J. Cowan,* Bertil E. Glader,* Connie J. Eaves, *1111 Allen C. Eaves,t1111 and Yuet Wai Kan1ltl Departments of*Pediatrics and "'Medicine and 1lHoward Hughes Medical Institute, University of California, San Francisco, San Francisco, California 94143; Departments of Pathology, **Pediatrics, and 111IMedicine, University ofBritish Columbia, and the §Terry Fox Laboratory, British Columbia Cancer Centre, Vancouver, British Columbia, Canada; Departments of'Genetics and "Pediatrics, Stanford University Medical School, Stanford, California 94303; and t*Department ofPediatrics, Washington University School of Medicine, St. Louis, Missouri 63110 Abstract cinogen exposure (3, 6). The age distribution of these de novo cases shows peaks in the first and fifth decades (6). Overall, Loss of expression of a tumor-suppressing gene is an attractive monosomy 7 or 7q- is identified in - 5% of de novo and in model to explain the cytogenetic and epidemiologic features of 40% of secondary cases of AML (1, 3-5). Although childhood cases of myelodysplasia and acute myelogenous leukemia bone marrow monosomy 7 is an uncommon disorder, it has (AML) associated with bone marrow monosomy 7 or partial been observed in two or more siblings at least seven times deletion of the long arm (7q-). We used probes from within the (7-10, Lange, B. J., personal communication, and our unpub- breakpoint region on 7q- chromosomes (7q22-34) that detect lished data).
    [Show full text]
  • The Cytogenetics of Hematologic Neoplasms 1 5
    The Cytogenetics of Hematologic Neoplasms 1 5 Aurelia Meloni-Ehrig that errors during cell division were the basis for neoplastic Introduction growth was most likely the determining factor that inspired early researchers to take a better look at the genetics of the The knowledge that cancer is a malignant form of uncon- cell itself. Thus, the need to have cell preparations good trolled growth has existed for over a century. Several biologi- enough to be able to understand the mechanism of cell cal, chemical, and physical agents have been implicated in division became of critical importance. cancer causation. However, the mechanisms responsible for About 50 years after Boveri’s chromosome theory, the this uninhibited proliferation, following the initial insult(s), fi rst manuscripts on the chromosome makeup in normal are still object of intense investigation. human cells and in genetic disorders started to appear, fol- The fi rst documented studies of cancer were performed lowed by those describing chromosome changes in neoplas- over a century ago on domestic animals. At that time, the tic cells. A milestone of this investigation occurred in 1960 lack of both theoretical and technological knowledge with the publication of the fi rst article by Nowell and impaired the formulations of conclusions about cancer, other Hungerford on the association of chronic myelogenous leu- than the visible presence of new growth, thus the term neo- kemia with a small size chromosome, known today as the plasm (from the Greek neo = new and plasma = growth). In Philadelphia (Ph) chromosome, to honor the city where it the early 1900s, the fundamental role of chromosomes in was discovered (see also Chap.
    [Show full text]