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The cancer biology of whole-chromosome instability

Oncogene volume 32, pages 4727–4736 (2013)Cite this article

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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.

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Acknowledgements

We thank Peter J Cook, Zvi Granot, Rozario I Thomas, Daniel Marks and Rocío Sotillo for critical reading of the manuscript. PHGD is supported by a Young Investigator Award from Alex’s Lemonade Stand Foundation and RB by the Breast Cancer Research Foundation.

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  1. Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    P H G Duijf & R Benezra

  2. The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia

    P H G Duijf

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Duijf, P., Benezra, R. The cancer biology of whole-chromosome instability. Oncogene 32, 4727–4736 (2013). https://doi.org/10.1038/onc.2012.616

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