PT  - JOURNAL ARTICLE
AU  - Daniel Temko
AU  - Ian PM Tomlinson
AU  - Simone Severini
AU  - Benjamin Schuster-Böckler
AU  - Trevor A Graham
TI  - The effects of mutational processes and selection on driver mutations across cancer types
AID  - 10.1101/149096
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 149096
4099  - http://biorxiv.org/content/early/2017/06/12/149096.short
4100  - http://biorxiv.org/content/early/2017/06/12/149096.full
AB  - Epidemiological evidence has long associated environmental mutagens with increased cancer risk. However, links between specific mutation-causing processes and the acquisition of individual driver mutations have remained obscure. Here we have used public cancer sequencing data to infer the independent effects of mutation and selection on driver mutation complement. First, we detect associations between a range of mutational processes, including those linked to smoking, ageing, APOBEC and DNA mismatch repair (MMR) and the presence of key driver mutations across cancer types. Second, we quantify differential selection between well-known alternative driver mutations, including differences in selection between distinct mutant residues in the same gene. These results show that while mutational processes play a large role in determining which driver mutations are present in a cancer, the role of selection frequently dominates.