Archives

  • 2019-10
  • 2019-11
  • 2020-03
  • 2020-07
  • 2020-08
  • b iframe width height src https www youtube com embed

    2020-07-26

    r> mors, respectively (Figs. 1D-F, K and L, and 4A and B). One such image appeared to show co-amplification of the ERBB2
    sequence with qPCR 17; this image is of particular inter-est because balanced increases in the numbers of ERBB2 and centromere 17 would have been interpreted as polysomy 17 by the 2007 criteria and so would have been excluded as a po-tential target of trastuzumab. However, more recent criteria suggest that increases in centromere-17 copy number may not necessarily represent chromosome-17 polysomy but instead may correspond to gain or amplification of the chromosome-17 centromeric region [23]. The present study suggested that gene amplification associated with centromeric regions may be a common type of amplification event, occurring as a subset of nearly all common amplifications.
    Amplicons in breast cancers 43
    Based the previous studies delineating the boundaries of the amplicons, common initial break sites in the amplicons are known to correspond to specific genes. Initially, genes lo-cated near each other in a chromosome region are co-amplified physically, but the amplicons of advanced cancers selected during tumor development may not be the same as the original amplicons, as shown in Fig. 2. In the present study, the pre-dominant type of amplicon found at 8p, 11q, and 17q was HSR, although 83% (26/31) of MYC amplifications occurred in non-HSR types. Marotta et al found neither duplicated seg-ments nor fragile sites within the 6-Mb region surrounding the MYC oncogene [4], suggesting a different mechanism for MYC amplification.
    In the current study, co-amplifications of the non-syntenic genes were observed in 35 tumors, as shown in Table 2. In each of eight of these tumors, the non-syntenic genes consti-tuted a single amplification unit (and thus a larger amplicon). Specifically, these events included the amplicons on 8p11 and 11q13 in six tumors; the amplicons on 8p11 and 17q11–
    12 in one case; and co-amplification of 17q11–12 and 16q22.1 in another case. The FISH images of intermingling of these non-syntenic genes in single clusters suggests to us that these events correspond to the early fusion of both genes by translocation, with subsequent amplification by BFB cycle.
    Acknowledgments
    Supplementary data
    References
    [2] Ethier SP. Identifying and validating causal genetic alterations in human breast cancer. Breast Cancer Res Treat 2003;78:285-7.
    [3] Coquelle A, Rozier L, Dutrillaux B, Debatisse M. Induction of multiple double-strand breaks within an hsr by meganucleaseI-SceI expression or fragile site activation leads to formation of double minutes and other chromosomal rearrangements. Oncogene 2002;21:7671-9. [4] Marotta M, Chen X, Inoshita A, et al. A common copy-number break-point of ERBB2 amplification in breast cancer colocalizes with a com-plex block of segmental duplications. Breast Cancer Res 2012;14:R150.
    [6] Shuster MI, Han L, Le Beau MM, et al. A consistent pattern of RIN1 re-arrangements in oral squamous cell carcinoma cell lines supports a breakage-fusion-bridge cycle model for 11q13 amplification. Genes  Chromosomes Cancer 2000;28:153-63.
    [7] Bernardino J, Gerbault-Seureau M, Zafrani B, et al. Homogeneously staining regions in 223 breast carcinomas: cytogenetic and clinicopatho-logical correlations. Br J Cancer 1998;78:1214-8.
    [9] Courjal F, Cuny M, Simony-Lafontaine J, et al. Mapping of DNA ampli-fications at 15 chromosomal localizations in 1875 breast tumors: defini-tion of phenotypic groups. Cancer Res 1997;57:4360-7.
    [10] Turner N, Pearson A, Sharpe R, et al. FGFR1 amplification drives endo-crine therapy resistance and is a therapeutic target in breast cancer. Can-cer Res 2010;70:2085-94.
    [12] Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast Cancer 2013. Ann Oncol 2013;24:2206-23.
    [13] Ooi A, Inokuchi M, Harada S, et al. Gene amplification of ESR1 in breast cancers–fact or fiction? A fluorescence in situ hybridization and multiplex ligation-dependent probe amplification study. J Pathol 2012;227:8-16. [14] Lee C, Wevrick R, Fisher RB, Ferguson-Smith MA, Lin CC. Human centromeric DNAs. Hum Genet 1997;100:291-304.
    [15] Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for hu-man epidermal growth factor receptor 2 testing in breast cancer: Ameri-can Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med 2014;138: 241-56.
    [16] Pearson A, Smyth E, Babina IS, et al. High-level clonal FGFR amplifica-tion and response to FGFR inhibition in a translational clinical trial. Can-cer Discov 2016;6:838-51.