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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


title = "Landscape of somatic mutations in 560 breast cancer whole-genome sequences",
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.",
keywords = "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",
author = "Serena Nik-Zainal and Helen Davies and Johan Staaf and Manasa Ramakrishna and Dominik Glodzik and Xueqing Zou and Inigo Martincorena and Alexandrov, {Ludmil B} and Sancha Martin and Wedge, {David C} and {Van Loo}, Peter and Ju, {Young Seok} and Marcel Smid and Brinkman, {Arie B} and Sandro Morganella and Aure, {Miriam R} and Lingj{\ae}rde, {Ole Christian} and Anita Langer{\o}d and Markus Ringn{\'e}r and Sung-Min Ahn and Sandrine Boyault and Brock, {Jane E} and Annegien Broeks and Adam Butler and Christine Desmedt and Luc Dirix and Serge Dronov and Aquila Fatima and Foekens, {John A} and Moritz Gerstung and Hooijer, {Gerrit K J} and Jang, {Se Jin} and Jones, {David R} and Hyung-Yong Kim and King, {Tari A} and Savitri Krishnamurthy and Lee, {Hee Jin} and Jeong-Yeon Lee and Yilong Li and Stuart McLaren and Andrew Menzies and Ville Mustonen and Sarah O'Meara and Iris Pauport{\'e} and Xavier Pivot and Purdie, {Colin A} and Keiran Raine and Kamna Ramakrishnan and Rodr{\'i}guez-Gonz{\'a}lez, {F Germ{\'a}n} and Gilles Romieu and Sieuwerts, {Anieta M} and Simpson, {Peter T} and Rebecca Shepherd and Lucy Stebbings and Stefansson, {Olafur A} and Jon Teague and Stefania Tommasi and Isabelle Treilleux and {Van den Eynden}, {Gert G} and Peter Vermeulen and Anne Vincent-Salomon and Lucy Yates and Carlos Caldas and {van't Veer}, Laura and Andrew Tutt and Stian Knappskog and Tan, {Benita Kiat Tee} and Jos Jonkers and {\AA}ke Borg and Ueno, {Naoto T} and Christos Sotiriou and Alain Viari and Futreal, {P Andrew} and Campbell, {Peter J} and Span, {Paul N} and {Van Laere}, Steven and Lakhani, {Sunil R} and Eyfjord, {Jorunn E} and Thompson, {Alastair M} and Ewan Birney and Stunnenberg, {Hendrik G} and {van de Vijver}, {Marc J} and Martens, {John W M} and Anne-Lise B{\o}rresen-Dale and Richardson, {Andrea L} and Gu Kong and Gilles Thomas and Stratton, {Michael R}",
year = "2016",
month = jun,
day = "2",
doi = "10.1038/nature17676",
language = "English",
volume = "534",
pages = "47--54",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7605",