Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 70,230 bioRxiv papers from 306,630 authors.
The Repertoire of Mutational Signatures in Human Cancer
Ludmil B Alexandrov,
Nicholas J. Haradhvala,
Mi Ni Huang,
Alvin WT Ng,
Kyle R Covington,
Dmitry A Gordenin,
Erik N. Bergstrom,
S M Ashiqul Islam,
Leszek J. Klimczak,
John R McPherson,
David A. Wheeler,
the PCAWG Mutational Signatures Working Group,
Steven G Rozen,
Michael R. Stratton
Posted 15 May 2018
bioRxiv DOI: 10.1101/322859
Posted 15 May 2018
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 systematic perspective on the repertoire of mutational processes contributing to the development of human cancer including a comprehensive reference set of mutational signatures in human cancer.
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