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

Research output: Contribution to journalArticle


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.


  • Serena Nik-Zainal
  • Helen Davies
  • 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
  • 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
  • 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
External organisations
  • Wellcome Trust Sanger Institute
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
  • Medical Genetics
  • Cell and Molecular Biology


  • Breast Neoplasms, Cohort Studies, DNA Mutational Analysis, DNA Replication, DNA, Neoplasm, Female, Genes, BRCA1, Genes, BRCA2, Genome, Human, Genomics, Humans, Male, Mutagenesis, Mutation, Mutation Rate, Oncogenes, Recombinational DNA Repair
Original languageEnglish
Pages (from-to)47-54
Number of pages8
Issue number7605
Publication statusPublished - 2016 Jun 2
Publication categoryResearch

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