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Oncogene. 2013 Oct;32(40):4727-36. doi: 10.1038/onc.2012.616. Epub 2013 Jan 14.

The cancer biology of whole-chromosome instability.

Author information

1
1] Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA [2] The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

Abstract

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.

PMID:
23318433
DOI:
10.1038/onc.2012.616
[Indexed for MEDLINE]

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