Distribution of breakpoints on chromosome 18 in breast, colorectal, and pancreatic carcinoma cell lines

被引:18
作者
Alsop, AE
Teschendorff, AE
Edwards, PAW
机构
[1] Univ Cambridge, Canc Genom Program, Hutchison MRC Res Ctr, Dept Pathol, Cambridge CB2 2XZ, England
[2] Univ Cambridge, Dept Oncol, Cambridge CB2 2XZ, England
关键词
D O I
10.1016/j.cancergencyto.2005.09.011
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Chromosome 18 is frequently rearranged in carcinomas. We explored the distribution of breakpoints affecting chromosome 18 by mapping 56 breakpoints in 26 carcinoma cell lines by fluorescence in situ hybridization (FISH) using bacterial artificial chromosomes (BACs) and band paints. The distribution of breaks among 18 intervals of chromosome 18 was significantly nonrandom. The interval spanning the centromere contained the greatest number of breaks and had the highest average copy number of any interval. There was a high density of breaks close to the centromere as well as actually within the centromere. A cluster of breaks encompassing SMAD4 was associated with the minimum average copy number, consistent with SMAD4 being a tumor suppressor gene. There may be another cluster of breaks around 18q12. We offer two interpretations of the concentration of breaks near the centromere. It may reflect selection for an oncogene near the centromere, or there may be an underlying bias of breakage toward the centromere. We show that the latter is predicted by a simple model that invokes random breakage following anchorage of some random point on the chromosome, or selection of breaks proximal to one of several tumor suppressor genes. (c) 2006 Elsevier Inc. All rights reserved.
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页码:97 / 109
页数:13
相关论文
共 71 条
  • [1] Spectral karyotyping suggests additional subsets of colorectal cancers characterized by pattern of chromosome rearrangement
    Abdel-Rahman, WM
    Katsura, K
    Rens, W
    Gorman, PA
    Sheer, D
    Bicknell, D
    Bodmer, WF
    Arends, MJ
    Wyllie, AH
    Edwards, PAW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (05) : 2538 - 2543
  • [2] BRATTAIN MG, 1981, CANCER RES, V41, P1751
  • [3] TISSUE TYPING THE HLA-A LOCUS FROM GENOMIC DNA BY SEQUENCE-SPECIFIC PCR - COMPARISON OF HLA GENOTYPE AND SURFACE EXPRESSION ON COLORECTAL TUMOR-CELL LINES
    BROWNING, MJ
    KRAUSA, P
    ROWAN, A
    BICKNELL, DC
    BODMER, JG
    BODMER, WF
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (07) : 2842 - 2845
  • [4] CAILLEAU R, 1978, IN VITRO CELL DEV B, V14, P911
  • [5] The Rho-associated protein kinase p160ROCK is required for centrosome positioning
    Chevrier, V
    Piel, M
    Collomb, N
    Saoudi, Y
    Frank, R
    Paintrand, M
    Narumiya, S
    Bornens, M
    Job, D
    [J]. JOURNAL OF CELL BIOLOGY, 2002, 157 (05) : 807 - 817
  • [6] IDENTIFICATION OF NOVEL GENES, SYT AND SSX, INVOLVED IN THE T(X18)(P11.2Q11.2) TRANSLOCATION FOUND IN HUMAN SYNOVIAL SARCOMA
    CLARK, J
    ROCQUES, PJ
    CREW, AJ
    GILL, S
    SHIPLEY, J
    CHAN, AML
    GUSTERSON, BA
    COOPER, CS
    [J]. NATURE GENETICS, 1994, 7 (04) : 502 - 508
  • [7] Molecular cytogenetic analysis of breast cancer cell lines
    Davidson, JM
    Gorringe, KL
    Chin, SF
    Orsetti, B
    Besret, C
    Courtay-Cahen, C
    Roberts, I
    Theillet, C
    Caldas, C
    Edwards, PAW
    [J]. BRITISH JOURNAL OF CANCER, 2000, 83 (10) : 1309 - 1317
  • [8] DEXTER DL, 1982, CANCER RES, V42, P2705
  • [9] Pathways of chromosome alteration in human epithelial cancers
    Dutrillaux, B
    [J]. ADVANCES IN CANCER RESEARCH, VOL 67, 1995, 67 : 59 - 82
  • [10] Further evidence to support the melanocytic origin of MDA-MB-435
    Ellison, G
    Klinowska, T
    Westwood, RFR
    Docter, E
    French, T
    Fox, JC
    [J]. JOURNAL OF CLINICAL PATHOLOGY-MOLECULAR PATHOLOGY, 2002, 55 (05): : 294 - 299