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The topography of mutational processes in breast cancer genomes

Morganella, Sandro (author)
European Bioinformatics Institute
Alexandrov, Ludmil B. (author)
Los Alamos National Laboratory
Glodzik, Dominik (author)
Wellcome Trust Sanger Institute
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Zou, Xueqing (author)
Wellcome Trust Sanger Institute
Davies, Helen (author)
Wellcome Trust Sanger Institute
Staaf, Johan (author)
Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
Sieuwerts, Anieta M. (author)
Erasmus University Medical Center
Brinkman, Arie B. (author)
Radboud University Nijmegen
Martin, Sancha (author)
Wellcome Trust Sanger Institute
Ramakrishna, Manasa (author)
Wellcome Trust Sanger Institute
Butler, Adam (author)
Wellcome Trust Sanger Institute
Kim, Hyung Yong (author)
Hanyang University
Borg, Åke (author)
Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
Sotiriou, Christos (author)
Institut Jules Bordet
Futreal, P. Andrew (author)
University of Texas
Campbell, Peter J. (author)
Wellcome Trust Sanger Institute
Span, Paul N. (author)
Radboud University Nijmegen
Van Laere, Steven (author)
University of Antwerp
Lakhani, Sunil R. (author)
Royal Brisbane and Women's Hospital
Eyfjord, Jorunn E. (author)
University of Iceland
Thompson, Alastair M. (author)
Ninewells Hospital and Medical School
Stunnenberg, Hendrik G. (author)
Radboud University Nijmegen
Van De Vijver, Marc J. (author)
Academic Medical Center of University of Amsterdam (AMC)
Martens, John W M (author)
Erasmus University Medical Center
Børresen-Dale, Anne Lise (author)
University of Oslo
Richardson, Andrea L. (author)
Dana-Farber Cancer Institute
Kong, Gu (author)
Hanyang University
Thomas, Gilles (author)
Centre Léon Bérard
Sale, Julian (author)
MRC Laboratory of Molecular Biology
Rada, Cristina (author)
MRC Laboratory of Molecular Biology
Stratton, Michael R. (author)
Wellcome Trust Sanger Institute
Birney, Ewan (author)
European Bioinformatics Institute
Nik-Zainal, Serena (author)
Cambridge University Hospitals NHS Foundation Trust
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 (creator_code:org_t)
2016-05-02
2016
English.
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
Related links:
http://dx.doi.org/10... (free)
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Somatic mutations in human cancers show unevenness in genomic distribution that correlate with aspects of genome structure and function. These mutations are, however, generated by multiple mutational processes operating through the cellular lineage between the fertilized egg and the cancer cell, each composed of specific DNA damage and repair components and leaving its own characteristic mutational signature on the genome. Using somatic mutation catalogues from 560 breast cancer whole-genome sequences, here we show that each of 12 base substitution, 2 insertion/deletion (indel) and 6 rearrangement mutational signatures present in breast tissue, exhibit distinct relationships with genomic features relating to transcription, DNA replication and chromatin organization. This signature-based approach permits visualization of the genomic distribution of mutational processes associated with APOBEC enzymes, mismatch repair deficiency and homologous recombinational repair deficiency, as well as mutational processes of unknown aetiology. Furthermore, it highlights mechanistic insights including a putative replication-dependent mechanism of APOBEC-related mutagenesis.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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