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跳跃性易位在实体瘤细胞系中很常见,并导致整个染色体臂的反复融合。

Jumping translocations are common in solid tumor cell lines and result in recurrent fusions of whole chromosome arms.

作者信息

Padilla-Nash H M, Heselmeyer-Haddad K, Wangsa D, Zhang H, Ghadimi B M, Macville M, Augustus M, Schröck E, Hilgenfeld E, Ried T

机构信息

Genetics Department, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

出版信息

Genes Chromosomes Cancer. 2001 Apr;30(4):349-63. doi: 10.1002/gcc.1101.

DOI:10.1002/gcc.1101
PMID:11241788
Abstract

Jumping translocations (JTs) and segmental jumping translocations (SJTs) are unbalanced translocations involving a donor chromosome arm or chromosome segment that has fused to multiple recipient chromosomes. In leukemia, where JTs have been predominantly observed, the donor segment (usually 1q) preferentially fuses to the telomere regions of recipient chromosomes. In this study, spectral karyotyping (SKY) and FISH analysis revealed 188 JTs and SJTs in 10 cell lines derived from carcinomas of the bladder, prostate, breast, cervix, and pancreas. Multiple JTs and SJTs were detected in each cell line and contributed to recurrent unbalanced whole-arm translocations involving chromosome arms 5p, 14q, 15q, 20q, and 21q. Sixty percent (113/188) of JT breakpoints occurred within centromere or pericentromeric regions of the recipient chromosomes, whereas only 12% of the breakpoints were located in the telomere regions. JT breakpoints of both donor and recipient chromosomes coincided with numerous fragile sites as well as viral integration sites for human DNA viruses. The JTs within each tumor cell line promoted clonal progression, leading to the acquisition of extra copies of the donated chromosome segments that often contained oncogenes (MYC, ABL, HER2/NEU, etc.), consequently resulting in tumor-specific genomic imbalances. Published 2001 Wiley-Liss, Inc.

摘要

跳跃易位(JTs)和节段性跳跃易位(SJTs)是不平衡易位,涉及与多个受体染色体融合的供体染色体臂或染色体片段。在主要观察到JTs的白血病中,供体片段(通常为1q)优先与受体染色体的端粒区域融合。在本研究中,光谱核型分析(SKY)和荧光原位杂交(FISH)分析在源自膀胱、前列腺、乳腺、宫颈和胰腺癌的10个细胞系中发现了188个JTs和SJTs。在每个细胞系中都检测到多个JTs和SJTs,它们导致了涉及染色体臂5p、14q、15q、20q和21q的复发性不平衡全臂易位。60%(113/188)的JT断点发生在受体染色体的着丝粒或着丝粒周围区域,而只有12%的断点位于端粒区域。供体和受体染色体的JT断点与许多脆性位点以及人类DNA病毒的病毒整合位点一致。每个肿瘤细胞系中的JTs促进了克隆进展,导致获得通常包含癌基因(MYC、ABL、HER2/NEU等)的供体染色体片段的额外拷贝,从而导致肿瘤特异性基因组失衡。2001年由Wiley-Liss公司出版。

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