The cancer biology of whole-chromosome instability

被引:94
作者
Duijf, P. H. G. [1 ,2 ]
Benezra, R. [1 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, New York, NY 10021 USA
[2] Univ Queensland, Diamantina Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia
关键词
whole-chromosome instability; aneuploidy; cancer biology; oncogene-induced mitotic stress; non-cell autonomous; tumor microenvironment; CELL-CYCLE PROGRESSION; AGING-ASSOCIATED PHENOTYPES; EARLY EMBRYONIC-DEVELOPMENT; TUMOR-SPECIFIC ANTIGENS; IN-SITU HYBRIDIZATION; DNA-DAMAGE; CENTROSOME AMPLIFICATION; GENOMIC INSTABILITY; SPINDLE ABNORMALITIES; MITOTIC CHECKPOINT;
D O I
10.1038/onc.2012.616
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
One form of chromosome instability (CIN), the recurrent missegregation of whole chromosomes during cell division (W-CIN), leads to aneuploidy. Although W-CIN is a hallmark of most cancers, mutations in genes involved in chromosome segregation are exceedingly rare. We discuss an oncogene-induced mitotic stress model that provides a mechanistic framework to explain this paradox. We also review the tumor-promoting and tumor-suppressing consequences of W-CIN. Importantly, we do this in the context of cancer as a complex systemic disease, rather than as a simple linearly progressing disorder that arises from a single abnormal cell population. Accordingly, we highlight the often neglected effects of W-CIN on key non-cell-autonomous entities, such as the immune system and the tumor microenvironment. Distinct tissue-specific susceptibilities to W-CIN-induced tumorigenesis and the clinical implications of W-CIN are also discussed.
引用
收藏
页码:4727 / 4736
页数:10
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