The mini-driver model of polygenic cancer evolution

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / pathology
  • Evolution, Molecular*
  • Humans
  • Mutation / genetics*
  • Neoplasm Proteins / genetics*
  • Neoplasms / genetics*
  • Neoplasms / pathology

Substances

  • Neoplasm Proteins