TY - JOUR
T1 - The repertoire of mutational signatures in human cancer
AU - PCAWG Mutational Signatures Working Group
AU - PCAWG Consortium
AU - Alexandrov, Ludmil B.
AU - Kim, Jaegil
AU - Haradhvala, Nicholas J.
AU - Mi, Ni Huang
AU - Ng, Alvin Wei Tian
AU - Yang, Wu
AU - Boot, Arnoud
AU - Covington, Kyle R.
AU - Gordenin, Dmitry A.
AU - Bergstrom, Erik N.
AU - Ashiqul Islam, S. M.
AU - Lopez-Bigas, Nuria
AU - Klimczak, Leszek J.
AU - McPherson, John R.
AU - Morganella, Sandro
AU - Sabarinathan, Radhakrishnan
AU - Wheeler, David A.
AU - Mustonen, Ville
AU - Getz, Gad
AU - Rozen, Steven G.
AU - Stratton, Michael R.
AU - Boutros, Paul
AU - Chan, Kin
AU - Fujimoto, Akihiro
AU - Kazanov, Marat
AU - Lawrence, Michael
AU - Martincorena, Iñigo
AU - Nakagawa, Hidewaki
AU - Polak, Paz
AU - Prokopec, Stephenie
AU - Roberts, Steven A.
AU - Saini, Natalie
AU - Shibata, Tatsuhiro
AU - Shiraishi, Yuichi
AU - Teh, Bin Tean
AU - Vázquez-García, Ignacio
AU - Yousif, Fouad
AU - Willie, Yu
AU - Aaltonen, Lauri A.
AU - Abascal, Federico
AU - Abeshouse, Adam
AU - Aburatani, Hiroyuki
AU - Adams, David J.
AU - Agrawal, Nishant
AU - Ahn, Keun Soo
AU - Ahn, Sung Min
AU - Aikata, Hiroshi
AU - Wang, Jiayin
AU - Yang, Huanming
AU - Ye, Kai
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/2/6
Y1 - 2020/2/6
N2 - Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature1. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses3–15, enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated—but distinct—DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.
AB - Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature1. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses3–15, enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated—but distinct—DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.
UR - https://www.scopus.com/pages/publications/85079072353
U2 - 10.1038/s41586-020-1943-3
DO - 10.1038/s41586-020-1943-3
M3 - 文章
C2 - 32025018
AN - SCOPUS:85079072353
SN - 0028-0836
VL - 578
SP - 94
EP - 101
JO - Nature
JF - Nature
IS - 7793
ER -
SDG 3 Good Health and Well-being