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The mini-driver model of polygenic cancer evolution

Nature Reviews Cancer volume 15, pages 680–685 (2015)Cite this article

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Abstract

Much of cancer genetics research has focused on the identification of the most-important somatic mutations ('major drivers') that cause tumour growth. However, many mutations found in cancer might not be major drivers or 'passenger' mutations, but instead might have relatively weak tumour-promoting effects. Our aim is to highlight the existence of these mutations (termed 'mini drivers' herein), as multiple mini-driver mutations might substitute for a major-driver change, especially in the presence of genomic instability or high mutagen exposure. The mini-driver model has clinical implications: for example, the effects of therapeutically targeting such genes may be limited. However, the main importance of the model lies in helping to provide a complete understanding of tumorigenesis, especially as we anticipate that an increasing number of mini-driver mutations will be found by cancer genome sequencing.

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Figure 1: Schemas of some mini-driver scenarios.
Figure 2: Ratio of NS/S mutations and mutational load in colorectal cancers according to their mutation burden.

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Acknowledgements

The authors are very grateful to T. Graham for comments and criticism. F.C.-G. and I.T. were supported by the Oxford National Institute for Health Research Comprehensive Biomedical Research Centre. Core funding to the Wellcome Trust Centre for Human Genetics was provided by the Wellcome Trust (090532/Z/09/Z).

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Authors and Affiliations

  1. Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK

    Francesc Castro-Giner & Ian Tomlinson

  2. Nuffield Department of Clinical Medicine, Henry Wellcome Building for Molecular Physiology, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    Peter Ratcliffe

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  1. Francesc Castro-Giner
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Correspondence to Peter Ratcliffe or Ian Tomlinson.

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Castro-Giner, F., Ratcliffe, P. & Tomlinson, I. The mini-driver model of polygenic cancer evolution. Nat Rev Cancer 15, 680–685 (2015). https://doi.org/10.1038/nrc3999

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