RT Journal Article
SR Electronic
T1 The Repertoire of Mutational Signatures in Human Cancer
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 322859
DO 10.1101/322859
A1 Alexandrov, Ludmil B
A1 Kim, Jaegil
A1 Haradhvala, Nicholas J
A1 Huang, Mi Ni
A1 Ng, Alvin WT
A1 Boot, Arnoud
A1 Covington, Kyle R
A1 Gordenin, Dmitry A
A1 Bergstrom, Erik
A1 Lopez-Bigas, Nuria
A1 Klimczak, Leszek J
A1 McPherson, John R
A1 Morganella, Sandro
A1 Sabarinathan, Radhakrishnan
A1 Wheeler, David A
A1 Mustonen, Ville
A1 Getz, Gad
A1 Rozen, Steven G
A1 Stratton, Michael R
A1 ,
YR 2018
UL http://biorxiv.org/content/early/2018/05/15/322859.abstract
AB Somatic mutations in cancer genomes are caused by multiple mutational processes each of which generates a characteristic mutational signature. Using 84,729,690 somatic mutations from 4,645 whole cancer genome and 19,184 exome sequences encompassing most cancer types we characterised 49 single base substitution, 11 doublet base substitution, four clustered base substitution, and 17 small insertion and deletion mutational signatures. The substantial dataset size compared to previous analyses enabled discovery of new signatures, separation of overlapping signatures and decomposition of signatures into components that may represent associated, but distinct, DNA damage, repair and/or replication mechanisms. Estimation of the contribution of each signature to the mutational catalogues of individual cancer genomes revealed associations with exogenous and endogenous exposures and defective DNA maintenance processes. However, many signatures are of unknown cause. This analysis provides a comprehensive perspective on the repertoire of mutational processes contributing to the development of human cancer.