Coleman W B, Tsongalis G J
Department of Pathology, University of North Carolina School of Medicine, Chapel Hill 27599, USA.
Anticancer Res. 1999 Nov-Dec;19(6A):4645-64.
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). Based upon this general observation, it has been suggested that cancer cells are genetically unstable, and that acquisition of genomic instability may represent an early step in the process of carcinogenesis and a general feature of many human tumors. Numerous studies have appeared that characterize the nature and frequency of occurrence of various molecular lesions in human tumors, and significant progress has been made towards the elucidation of the molecular mechanisms that govern genetic stability in normal cells and genetic instability in neoplastic cells. In this review, we examine the evidence that genomic instability plays a significant role in the genesis of various human tumors. Furthermore, we consider the possible molecular pathways to tumorigenesis in humans and how different forms of genetic instability may impact upon these pathways.
肿瘤细胞通常具有众多基因组损伤，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明显结构异常（大规模缺失、重排、基因扩增）。基于这一普遍观察结果，有人提出癌细胞具有遗传不稳定性，并且获得基因组不稳定性可能代表致癌过程中的早期步骤以及许多人类肿瘤的一个普遍特征。已经出现了大量研究，这些研究描述了人类肿瘤中各种分子损伤的性质和发生频率，并且在阐明控制正常细胞遗传稳定性和肿瘤细胞遗传不稳定性的分子机制方面取得了重大进展。在这篇综述中，我们研究了基因组不稳定性在各种人类肿瘤发生中起重要作用的证据。此外，我们考虑了人类肿瘤发生的可能分子途径，以及不同形式的遗传不稳定性如何影响这些途径。
