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Nat Rev Cancer. 2015 Nov;15(11):680-5. doi: 10.1038/nrc3999. Epub 2015 Oct 12.

The mini-driver model of polygenic cancer evolution.

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Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Henry Wellcome Building for Molecular Physiology, Nuffield Department of Clinical Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.


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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