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Cancer genomics

The driving force of cancer evolution

Nature Reviews Genetics volume 18, page 703 (2017)Cite this article

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Cancer develops from somatically accumulating mutations, but not all mutations drive tumorigenesis. Driver mutations have been positively selected for the growth advantage they confer. By contrast, unselected, passenger mutations have no fitness effects and thus do not contribute to cancer development.

Quantitative estimates of the number of driver mutations needed for cancer to develop were lacking. Martincorena et al. sought to address this issue by calculating the ratio of non-synonymous to synonymous substitutions (dN/dS) across 7,664 tumours from 29 cancer types. Quantifying positive and negative selection using molecular evolution methods allowed the authors to directly estimate any excess or deficit of mutations compared with the number expected under neutrality.

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References

  1. Martincorena, I. et al. Universal patterns of selection in cancer and somatic tissues. Cell http://dx.doi.org/10.1016/j.cell.2017.09.042 (2017)

  2. Campbell, B. B. et al. Comprehensive analysis of hypermutation in human cancer. Cell http://dx.doi.org/10.1016/j.cell.2017.09.048 (2017)

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Authors
  1. Linda Koch
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Koch, L. The driving force of cancer evolution. Nat Rev Genet 18, 703 (2017). https://doi.org/10.1038/nrg.2017.95

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