title: 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.
authors.affiliation: Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Francesc
authors.initials: F
authors.lastname: Castro-Giner
authors.affiliation: Henry Wellcome Building for Molecular Physiology, Nuffield Department of Clinical Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Ratcliffe
authors.affiliation: Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Tomlinson
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D019143:Evolution, Molecular; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins