Landscape of somatic mutations in 560 breast cancer whole-genome sequences.

Nature ·第 534 卷 ·第 7605 期 ·2016-06-28

Nik-Zainal Serena, Davies Helen, Staaf Johan, Ramakrishna Manasa, Glodzik Dominik, Zou Xueqing, Martincorena Inigo, Alexandrov Ludmil B, Martin Sancha, Wedge David C, Van Loo Peter, Ju Young Seok, Smid Marcel, Brinkman Arie B, Morganella Sandro, Aure Miriam R, Lingjærde Ole Christian, Langerød Anita, Ringnér Markus, Ahn Sung-Min, Boyault Sandrine, Brock Jane E, Broeks Annegien, Butler Adam, Desmedt Christine, Dirix Luc, Dronov Serge, Fatima Aquila, Foekens John A, Gerstung Moritz, Hooijer Gerrit K J, Jang Se Jin, Jones David R, Kim Hyung-Yong, King Tari A, Krishnamurthy Savitri, Lee Hee Jin, Lee Jeong-Yeon, Li Yilong, McLaren Stuart, Menzies Andrew, Mustonen Ville, O'Meara Sarah, Pauporté Iris, Pivot Xavier, Purdie Colin A, Raine Keiran, Ramakrishnan Kamna, Rodríguez-González F Germán, Romieu Gilles, Sieuwerts Anieta M, Simpson Peter T, Shepherd Rebecca, Stebbings Lucy, Stefansson Olafur A, Teague Jon, Tommasi Stefania, Treilleux Isabelle, Van den Eynden Gert G, Vermeulen Peter, Vincent-Salomon Anne, Yates Lucy, Caldas Carlos, van't Veer Laura, Tutt Andrew, Knappskog Stian, Tan Benita Kiat Tee, Jonkers Jos, Borg Åke, Ueno Naoto T, Sotiriou Christos, Viari Alain, Futreal P Andrew, Campbell Peter J, Span Paul N, Van Laere Steven, Lakhani Sunil R, Eyfjord Jorunn E, Thompson Alastair M, Birney Ewan, Stunnenberg Hendrik G, van de Vijver Marc J, Martens John W M, Børresen-Dale Anne-Lise, Richardson Andrea L, Kong Gu, Thomas Gilles, Stratton Michael R

摘要

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.

文献信息

期刊

Nature

期刊简称

Nature

ISSN

0028-0836

发表日期

2016-06-28

收录日期

2016-06-02

更新日期

2016-12-02

语言

英语

国家/地区

England

NLM ID

0410462

外部链接

PubMed 原文查看期刊详情

分析服务

Landscape of somatic mutations in 560 breast cancer whole-genome sequences.

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