The mini-driver model of polygenic cancer evolution.

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.