Emdad Luni, Sarkar Devanand, Su Zao-Zhong, Fisher Paul B
Department of Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians and Surgeons, New York, New York 10032, USA.
Front Biosci. 2005 Jan 1;10:728-42. doi: 10.2741/1567.
The carcinogenic process is multistep in terms of its etiology and multifactor in terms of its evolution. In this context, the temporal accumulation of multiple genetic changes during multistage carcinogenesis that can be mediated at least in part by genomic instability may represent crucial components of tumor cell evolution. Evidence is accumulating indicating a close link between genomic instability and cancer initiation and progression. Neoplastic cells typically possess numerous genomic lesions, which may include sequence alterations (point mutations, small deletions, and insertions) and/or gross structural abnormalities in one or more chromosomes (large-scale deletions, rearrangements, gene amplifications). Furthermore karyotypic alterations, including whole chromosome loss or gain, ploidy changes (aneuploidy and polyploidy) and a variety of chromosome aberrations are common in tumor cells. Genomic instability also involves mitotic defects associated with centrosome abnormalities. However, the question of whether abnormal centrosomes cause genomic instability or develop secondary to other changes has not been conclusively resolved. In this review, the recent studies investigating genomic instability and aneuploidy in human cancer, centrosome amplification and the role of centrosomal duplication in chromosomal mis-segregetion, and genes implicated in regulating chromosome segregation, centrosomal amplification and progression in cancer cells are discussed.
致癌过程在病因学上是多步骤的，在其演变过程中是多因素的。在这种情况下，多阶段致癌过程中多种基因变化的时间积累至少部分可由基因组不稳定介导，这可能代表肿瘤细胞演变的关键组成部分。越来越多的证据表明基因组不稳定与癌症的发生和发展密切相关。肿瘤细胞通常具有大量的基因组损伤，这可能包括序列改变（点突变、小缺失和插入）和/或一条或多条染色体中的严重结构异常（大规模缺失、重排、基因扩增）。此外，核型改变，包括整条染色体的丢失或增加、倍性变化（非整倍体和多倍体）以及各种染色体畸变在肿瘤细胞中很常见。基因组不稳定还涉及与中心体异常相关的有丝分裂缺陷。然而，异常中心体是否导致基因组不稳定或继发于其他变化的问题尚未得到最终解决。在这篇综述中，讨论了最近关于人类癌症中基因组不稳定和非整倍体、中心体扩增以及中心体复制在染色体错误分离中的作用，以及涉及调节染色体分离、中心体扩增和癌细胞进展的基因的研究。
