The topography of mutational processes in breast cancer genomes

Morganella, Sandro, Alexandrov, Ludmil B., Glodzik, Dominik, Zou, Xueqing, Davies, Helen, Staaf, Johan, Sieuwerts, Anieta M., Brinkman, Arie B., Martin, Sancha, Ramakrishna, Manasa, Butler, Adam, Kim, Hyung-Yong, Borg, Ake, Sotiriou, Christos, Futreal, P. Andrew, Campbell, Peter J., Span, Paul N., Van Laere, Steven, Lakhani, Sunil R., Eyfjord, Jorunn E., Thompson, Alastair M., Stunnenberg, Hendrik G., van de Vijver, Marc J., Martens, John W. M., Borresen-Dale, Anne-Lise, Richardson, Andrea L., Kong, Gu, Thomas, Gilles, Sale, Julian, Rada, Cristina, Stratton, Michael R., Birney, Ewan and Nik-Zainal, Serena (2016) The topography of mutational processes in breast cancer genomes. Nature Communications, 7 11383: 1-11. doi:10.1038/ncomms11383

Author Morganella, Sandro
Alexandrov, Ludmil B.
Glodzik, Dominik
Zou, Xueqing
Davies, Helen
Staaf, Johan
Sieuwerts, Anieta M.
Brinkman, Arie B.
Martin, Sancha
Ramakrishna, Manasa
Butler, Adam
Kim, Hyung-Yong
Borg, Ake
Sotiriou, Christos
Futreal, P. Andrew
Campbell, Peter J.
Span, Paul N.
Van Laere, Steven
Lakhani, Sunil R.
Eyfjord, Jorunn E.
Thompson, Alastair M.
Stunnenberg, Hendrik G.
van de Vijver, Marc J.
Martens, John W. M.
Borresen-Dale, Anne-Lise
Richardson, Andrea L.
Kong, Gu
Thomas, Gilles
Sale, Julian
Rada, Cristina
Stratton, Michael R.
Birney, Ewan
Nik-Zainal, Serena
Title The topography of mutational processes in breast cancer genomes
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2016-05-02
Year available 2016
Sub-type Article (original research)
DOI 10.1038/ncomms11383
Open Access Status DOI
Volume 7
Issue 11383
Start page 1
End page 11
Total pages 11
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2017
Language eng
Abstract 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
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