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dc.contributor.authorMorganella, Sandro
dc.contributor.authorAlexandrov, Ludmil B
dc.contributor.authorGlodzik, Dominik
dc.contributor.authorZou, Xueqing
dc.contributor.authorDavies, Helen
dc.contributor.authorStaaf, Johan
dc.contributor.authorSieuwerts, Anieta M
dc.contributor.authorBrinkman, Arie B
dc.contributor.authorMartin, Sancha
dc.contributor.authorRamakrishna, Manasa
dc.contributor.authorButler, Adam
dc.contributor.authorKim, Hyung-Yong
dc.contributor.authorBorg, Åke
dc.contributor.authorSotiriou, Christos
dc.contributor.authorFutreal, P Andrew
dc.contributor.authorCampbell, Peter J
dc.contributor.authorSpan, Paul N
dc.contributor.authorVan Laere, Steven
dc.contributor.authorLakhani, Sunil R
dc.contributor.authorEyfjord, Jorunn E
dc.contributor.authorThompson, Alastair M
dc.contributor.authorStunnenberg, Hendrik G
dc.contributor.authorvan de Vijver, Marc J
dc.contributor.authorMartens, John WM
dc.contributor.authorBørresen-Dale, Anne-Lise
dc.contributor.authorRichardson, Andrea L
dc.contributor.authorKong, Gu
dc.contributor.authorThomas, Gilles
dc.contributor.authorSale, Julian
dc.contributor.authorRada, Cristina
dc.contributor.authorStratton, Michael R
dc.contributor.authorBirney, Ewan
dc.contributor.authorNik-Zainal, Serena
dc.date.accessioned2018-11-01T14:02:46Z
dc.date.available2018-11-01T14:02:46Z
dc.date.issued2016-05-02
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/284500
dc.description.abstractSomatic 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.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectChromatin
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectDNA Damage
dc.subjectApolipoproteins B
dc.subjectSequence Analysis, DNA
dc.subjectDNA Repair
dc.subjectDNA Replication
dc.subjectTranscription, Genetic
dc.subjectMutagenesis
dc.subjectMutation
dc.subjectGenome, Human
dc.subjectFemale
dc.subjectMCF-7 Cells
dc.titleThe topography of mutational processes in breast cancer genomes.
dc.typeArticle
prism.publicationDate2016
prism.publicationNameNat Commun
prism.startingPage11383
prism.volume7
dc.identifier.doi10.17863/CAM.31875
dcterms.dateAccepted2016-03-18
rioxxterms.versionofrecord10.1038/ncomms11383
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-05-02
dc.contributor.orcidSpan, Paul N [0000-0002-1930-6638]
dc.contributor.orcidLakhani, Sunil R [0000-0003-1879-2555]
dc.contributor.orcidRada, Cristina [0000-0003-4898-5550]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Review
pubs.funder-project-idEuropean Commission (242006)
cam.issuedOnline2016-05-02


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International