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

Serena Nik-Zainal (), Helen 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, Annegien 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 T. 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 and Michael R. Stratton ()
Additional contact information
Serena Nik-Zainal: Wellcome Trust Sanger Institute, Hinxton
Helen Davies: Wellcome Trust Sanger Institute, Hinxton
Johan Staaf: Lund University
Manasa Ramakrishna: Wellcome Trust Sanger Institute, Hinxton
Dominik Glodzik: Wellcome Trust Sanger Institute, Hinxton
Xueqing Zou: Wellcome Trust Sanger Institute, Hinxton
Inigo Martincorena: Wellcome Trust Sanger Institute, Hinxton
Ludmil B. Alexandrov: Wellcome Trust Sanger Institute, Hinxton
Sancha Martin: Wellcome Trust Sanger Institute, Hinxton
David C. Wedge: Wellcome Trust Sanger Institute, Hinxton
Peter Van Loo: Wellcome Trust Sanger Institute, Hinxton
Young Seok Ju: Wellcome Trust Sanger Institute, Hinxton
Marcel Smid: Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Erasmus University Medical Center
Arie B. Brinkman: Radboud University, Faculty of Science
Sandro Morganella: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus
Miriam R. Aure: Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital
Ole Christian Lingjærde: K. G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo
Anita Langerød: Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital
Markus Ringnér: Lund University
Sung-Min Ahn: Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center
Sandrine Boyault: Translational Research Lab, Centre Léon Bérard, 28, rue Laënnec
Jane E. Brock: Brigham and Women’s Hospital
Annegien Broeks: The Netherlands Cancer Institute
Adam Butler: Wellcome Trust Sanger Institute, Hinxton
Christine Desmedt: Breast Cancer Translational Research Laboratory, Université Libre de Bruxelles, Institut Jules Bordet
Luc Dirix: Translational Cancer Research Unit, Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp
Serge Dronov: Wellcome Trust Sanger Institute, Hinxton
Aquila Fatima: Dana-Farber Cancer Institute
John A. Foekens: Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Erasmus University Medical Center
Moritz Gerstung: Wellcome Trust Sanger Institute, Hinxton
Gerrit K. J. Hooijer: Academic Medical Center
Se Jin Jang: Asan Medical Center, College of Medicine, Ulsan University
David R. Jones: Wellcome Trust Sanger Institute, Hinxton
Hyung-Yong Kim: College of Medicine, Hanyang University
Tari A. King: Memorial Sloan Kettering Cancer Center
Savitri Krishnamurthy: Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard.
Hee Jin Lee: Asan Medical Center, College of Medicine, Ulsan University
Jeong-Yeon Lee: Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University
Yilong Li: Wellcome Trust Sanger Institute, Hinxton
Stuart McLaren: Wellcome Trust Sanger Institute, Hinxton
Andrew Menzies: Wellcome Trust Sanger Institute, Hinxton
Ville Mustonen: Wellcome Trust Sanger Institute, Hinxton
Sarah O’Meara: Wellcome Trust Sanger Institute, Hinxton
Iris Pauporté: Institut National du Cancer
Xavier Pivot: University Hospital of Minjoz, INSERM UMR 1098, Bd Fleming
Colin A. Purdie: Ninewells Hospital and Medical School
Keiran Raine: Wellcome Trust Sanger Institute, Hinxton
Kamna Ramakrishnan: Wellcome Trust Sanger Institute, Hinxton
F. Germán Rodríguez-González: Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Erasmus University Medical Center
Gilles Romieu: Oncologie Sénologie, ICM Institut Régional du Cancer
Anieta M. Sieuwerts: Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Erasmus University Medical Center
Peter T. Simpson: The University of Queensland, UQ Centre for Clinical Research and School of Medicine
Rebecca Shepherd: Wellcome Trust Sanger Institute, Hinxton
Lucy Stebbings: Wellcome Trust Sanger Institute, Hinxton
Olafur A. Stefansson: Cancer Research Laboratory, Faculty of Medicine, University of Iceland
Jon Teague: Wellcome Trust Sanger Institute, Hinxton
Stefania Tommasi: IRCCS Istituto Tumori “Giovanni Paolo II”
Isabelle Treilleux: Centre Léon Bérard, 28 rue Laënnec
Gert G. Van den Eynden: Translational Cancer Research Unit, Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp
Peter Vermeulen: Translational Cancer Research Unit, Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp
Anne Vincent-Salomon: Institut Curie, Paris Sciences Lettres University, 26 rue d’Ulm
Lucy Yates: Wellcome Trust Sanger Institute, Hinxton
Carlos Caldas: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way
Laura van’t Veer: The Netherlands Cancer Institute
Andrew Tutt: Breast Cancer Now Research Unit, King’s College London
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: Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard.
Christos Sotiriou: Breast Cancer Translational Research Laboratory, Université Libre de Bruxelles, Institut Jules Bordet
Alain Viari: Equipe Erable, INRIA Grenoble-Rhône-Alpes
P. Andrew Futreal: Wellcome Trust Sanger Institute, Hinxton
Peter J. Campbell: Wellcome Trust Sanger Institute, Hinxton
Paul N. Span: Radboud University Medical Center
Steven Van Laere: Translational Cancer Research Unit, Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp
Sunil R. Lakhani: The University of Queensland, UQ Centre for Clinical Research and School of Medicine
Jorunn E. Eyfjord: Cancer Research Laboratory, Faculty of Medicine, University of Iceland
Alastair M. Thompson: Ninewells Hospital and Medical School
Ewan Birney: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus
Hendrik G. Stunnenberg: Radboud University, Faculty of Science
Marc J. van de Vijver: Academic Medical Center
John W. M. Martens: Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Erasmus University Medical Center
Anne-Lise Børresen-Dale: Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital
Andrea L. Richardson: Brigham and Women’s Hospital
Gu Kong: College of Medicine, Hanyang University
Gilles Thomas: Synergie Lyon Cancer, Centre Léon Bérard, 28 rue Laënnec
Michael R. Stratton: Wellcome Trust Sanger Institute, Hinxton

Nature, 2016, vol. 534, issue 7605, 47-54

Abstract: 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.

Date: 2016
References: Add references at CitEc
Citations: View citations in EconPapers (32)

Downloads: (external link)
https://www.nature.com/articles/nature17676 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:534:y:2016:i:7605:d:10.1038_nature17676

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature17676

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().