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非整倍体会引发癌症吗?

Does aneuploidy cause cancer?

作者信息

Weaver Beth A A, Cleveland Don W

机构信息

Ludwig Institute for Cancer Research, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0670, USA.

出版信息

Curr Opin Cell Biol. 2006 Dec;18(6):658-67. doi: 10.1016/j.ceb.2006.10.002. Epub 2006 Oct 12.

Abstract

Aneuploidy has been recognized as a common characteristic of cancer cells for >100 years. Aneuploidy frequently results from errors of the mitotic checkpoint, the major cell cycle control mechanism that acts to prevent chromosome missegregation. The mitotic checkpoint is often compromised in human tumors, although not as a result of germline mutations in genes encoding checkpoint proteins. Less obviously, aneuploidy of whole chromosomes rapidly results from mutations in genes encoding several tumor suppressors and DNA mismatch repair proteins, suggesting cooperation between mechanisms of tumorigenesis that were previously thought to act independently. Cumulatively, the current evidence suggests that aneuploidy promotes tumorigenesis, at least at low frequency, but a definitive test has not yet been reported.

摘要

非整倍体作为癌细胞的一个常见特征已被认识超过100年。非整倍体常因有丝分裂检查点出错所致,有丝分裂检查点是防止染色体错误分离的主要细胞周期控制机制。人类肿瘤中,有丝分裂检查点常受损,尽管并非由于编码检查点蛋白的基因发生种系突变。不太明显的是,编码几种肿瘤抑制因子和DNA错配修复蛋白的基因突变会迅速导致整条染色体的非整倍体,这表明以前认为独立发挥作用的肿瘤发生机制之间存在协同作用。总体而言,目前的证据表明非整倍体至少在低频率时会促进肿瘤发生,但尚未有确定性的试验报告。

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