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

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

doi:10.1038/nature17676

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

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

Serena Nik-Zainal, Helen R. Davies, Johan Staaf, Manasa Ramakrishna, Dominik Glodzik, Xueqing Zou, Inigo Martincorena, Ludmil B. Alexandrov, Sancha Martin, David C. Wedge, …

Nature, Vol.534(7605), pp.47 - 54

2016

DOI: https://doi.org/10.1038/nature17676

Abstract

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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Title: Landscape of somatic mutations in 560 breast cancer whole-genome sequences
Creators - without role: Serena Nik-Zainal - Wellcome Sanger Institute
Helen R. Davies - Wellcome Sanger Institute
Johan Staaf - Lund University
Manasa Ramakrishna - Wellcome Sanger Institute
Dominik Glodzik - Wellcome Sanger Institute
Xueqing Zou - Wellcome Sanger Institute
Inigo Martincorena - Wellcome Sanger Institute
Ludmil B. Alexandrov - Wellcome Sanger Institute
Sancha Martin - Wellcome Sanger Institute
David C. Wedge - Wellcome Sanger Institute
Peter van Loo - Wellcome Sanger Institute
Young Seok Ju - Wellcome Sanger Institute
Marcel Smid - Erasmus MC Cancer Institute
Arie B. Brinkman - Radboud University Nijmegen
Sandro Morganella - European Bioinformatics Institute
Miriam R. Aure - Oslo University Hospital
Ole Christian Lingjærde - University of Oslo
Anita Langerød - Oslo University Hospital
Markus Ringnér - Lund University
Sung-Min Ahn - Gachon University
Sandrine Boyault - Centre Léon Bérard
Jane E. Brock - Brigham and Women's Hospital
Anne Broeks - Netherlands Cancer Institute
Adam Butler - Wellcome Sanger Institute
Christine Desmedt - Institut Jules Bordet
Luc Dirix - University of Antwerp
Serge Dronov - Wellcome Sanger Institute
Aquila Fatima - Dana-Farber Cancer Institute
John A. Foekens - Erasmus MC
Moritz Gerstung - Wellcome Sanger Institute
Gerrit K. J. Hooijer - Academic Medical Center
Se Jin Jang - Asan Medical Center
David R. Jones - Wellcome Sanger Institute
Hyung-Yong Kim - Hanyang University
Tari A. King - Memorial Sloan Kettering Cancer Center
Savitri Krishnamurthy - The University of Texas MD Anderson Cancer Center
Hee Jin Lee - Asan Medical Center
Jeong-Yeon Lee - Department of Geriatric Medicine [Singapore] (Alexandra Hospital)
Yilong Li - Wellcome Sanger Institute
Stuart Mclaren - Wellcome Sanger Institute
Andrew Menzies - Wellcome Sanger Institute
Ville Mustonen - Wellcome Sanger Institute
Sarah O’meara - Wellcome Sanger Institute
Iris Pauporté - Institut National du Cancer
Xavier Pivot - Centre Hospitalier Universitaire de Besançon
Colin A. Purdie - Ninewells Hospital
Keiran Raine - Wellcome Sanger Institute
Kamna Ramakrishnan - Wellcome Sanger Institute
F. Germán Rodríguez-González - Erasmus MC Cancer Institute
Gilles Romieu - Université de Montpellier, Institut de Recherche en Cancérologie de Montpellier - IRCM
Anieta M. Sieuwerts - Erasmus MC Cancer Institute
Peter Simpson - University of Queensland
Rebecca Shepherd - Wellcome Sanger Institute
Lucy Stebbings - Wellcome Sanger Institute
Olafur A. Stefansson - University of Iceland
Jon Teague - Wellcome Sanger Institute
Stefania Tommasi - Istituti di Ricovero e Cura a Carattere Scientifico
Isabelle Treilleux - Centre Léon Bérard
Gert G. van den Eynden - University of Antwerp
Peter Vermeulen - University of Antwerp
Anne Vincent-Salomon - Inserm
Lucy Yates - Wellcome Sanger Institute
Carlos Caldas - University of Cambridge
Laura Van’t Veer - Oncode Institute
Andrew Tutt - Breast Cancer Now
Stian Knappskog - University of Bergen
Benita Kiat Tee Tan - National Cancer Centre Singapore
Jos Jonkers - The Netherlands Cancer Institute
Åke Borg - Lund University
Naoto T. Ueno - The University of Texas MD Anderson Cancer Center
Christos Sotiriou - Institut Jules Bordet
Alain Viari - Centre Inria de l'Université Grenoble Alpes
P. Andrew Futreal - The University of Texas MD Anderson Cancer Center
Peter J. Campbell - Wellcome Sanger Institute
Paul N. Span - Radboud University Nijmegen
Steven van Laere - University of Antwerp
Sunil R. Lakhani - University of Queensland
Jorunn E. Eyfjord - University of Iceland
Alastair M. Thompson - Ninewells Hospital
Ewan Birney - European Bioinformatics Institute
Hendrik G. Stunnenberg - Radboud University Nijmegen
Marc J. van de Vijver - Academic Medical Center
John W. M. Martens - Erasmus MC Cancer Institute
Anne-Lise Børresen-Dale - Oslo University Hospital
Andrea L. Richardson - Dana-Farber Cancer Institute
Gu Kong - Hanyang University
Gilles Thomas - Fondation Synergie Lyon Cancer [Lyon]
Michael R. Stratton - Wellcome Sanger Institute
Publication Details: Nature, Vol.534(7605), pp.47 - 54
Identifiers: 9937422409311
Academic Unit: Institut de Recherche en Cancérologie de Montpellier - IRCM
Language: English
Resource Type: Journal article
Local Fields: hal-01388447