Landscape of somatic mutations in 560 breast cancer whole-genome sequences.
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Date
2016-06-02ICR Author
Author
Nik-Zainal, S
Davies, H
Staaf, J
Ramakrishna, M
Glodzik, D
Zou, X
Martincorena, I
Alexandrov, LB
Martin, S
Wedge, DC
Van Loo, P
Ju, YS
Smid, M
Brinkman, AB
Morganella, S
Aure, MR
Lingjærde, OC
Langerød, A
Ringnér, M
Ahn, S-M
Boyault, S
Brock, JE
Broeks, A
Butler, A
Desmedt, C
Dirix, L
Dronov, S
Fatima, A
Foekens, JA
Gerstung, M
Hooijer, GKJ
Jang, SJ
Jones, DR
Kim, H-Y
King, TA
Krishnamurthy, S
Lee, HJ
Lee, J-Y
Li, Y
McLaren, S
Menzies, A
Mustonen, V
O'Meara, S
Pauporté, I
Pivot, X
Purdie, CA
Raine, K
Ramakrishnan, K
Rodríguez-González, FG
Romieu, G
Sieuwerts, AM
Simpson, PT
Shepherd, R
Stebbings, L
Stefansson, OA
Teague, J
Tommasi, S
Treilleux, I
Van den Eynden, GG
Vermeulen, P
Vincent-Salomon, A
Yates, L
Caldas, C
van't Veer, L
Tutt, A
Knappskog, S
Tan, BKT
Jonkers, J
Borg, Å
Ueno, NT
Sotiriou, C
Viari, A
Futreal, PA
Campbell, PJ
Span, PN
Van Laere, S
Lakhani, SR
Eyfjord, JE
Thompson, AM
Birney, E
Stunnenberg, HG
van de Vijver, MJ
Martens, JWM
Børresen-Dale, A-L
Richardson, AL
Kong, G
Thomas, G
Stratton, MR
Type
Journal Article
Metadata
Show full item recordAbstract
We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
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Subject
Humans
Breast Neoplasms
DNA, Neoplasm
Cohort Studies
DNA Mutational Analysis
Genomics
DNA Replication
Mutagenesis
Mutation
Genes, BRCA1
Genes, BRCA2
Oncogenes
Genome, Human
Female
Male
Mutation Rate
Recombinational DNA Repair
Language
eng
Date accepted
2016-03-17
License start date
2016-06
Citation
Nature, 2016, 534 (7605), pp. 47 - 54
Publisher
NATURE PUBLISHING GROUP