RT Journal Article
SR Electronic
T1 The effects of mutational processes and selection on driver mutations across cancer types
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 149096
DO 10.1101/149096
A1 Daniel Temko
A1 Ian PM Tomlinson
A1 Simone Severini
A1 Benjamin Schuster-Böckler
A1 Trevor A Graham
YR 2017
UL http://biorxiv.org/content/early/2017/06/12/149096.abstract
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.