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  • Perspectives
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Human cancers express mutator phenotypes: origin, consequences and targeting

Abstract

Recent data on DNA sequencing of human tumours have established that cancer cells contain thousands of mutations. These data support the concept that cancer cells express a mutator phenotype. This Perspective considers the evidence supporting the mutator phenotype hypothesis, the origin and consequences of a mutator phenotype, the implications for personalized medicine and the feasibility of ablating tumours by error catastrophe.

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Figure 1: Cascade of mutations during tumour progression.
Figure 2: Dissemination of metastasis early and late during tumour progression.

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Acknowledgements

I thank E. Fox, B. Preston, A. Kamath, M. Horwitz and S. Nishimura for critical reading and D. Lim for constructing the figures. I am indebted to present and former members of our laboratory for establishing some of the evidence presented and for daily discussions. This work was supported by Grants from the US National Cancer Institute (CA-102029, CA-105802 and CA-77852) and the US National Institute of Aging (AG-033061).

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Loeb, L. Human cancers express mutator phenotypes: origin, consequences and targeting. Nat Rev Cancer 11, 450–457 (2011). https://doi.org/10.1038/nrc3063

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