Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer.

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cam.issuedOnline2014-04-13
dc.contributor.authorNik-Zainal, Serena
dc.contributor.authorWedge, David C
dc.contributor.authorAlexandrov, Ludmil B
dc.contributor.authorPetljak, Mia
dc.contributor.authorButler, Adam P
dc.contributor.authorBolli, Niccolo
dc.contributor.authorDavies, Helen R
dc.contributor.authorKnappskog, Stian
dc.contributor.authorMartin, Sancha
dc.contributor.authorPapaemmanuil, Elli
dc.contributor.authorRamakrishna, Manasa
dc.contributor.authorShlien, Adam
dc.contributor.authorSimonic, Ingrid
dc.contributor.authorXue, Yali
dc.contributor.authorTyler-Smith, Chris
dc.contributor.authorCampbell, Peter J
dc.contributor.authorStratton, Michael R
dc.contributor.orcidNik-Zainal Abidin, Serena [0000-0001-5054-1727]
dc.date.accessioned2019-08-02T11:13:14Z
dc.date.available2019-08-02T11:13:14Z
dc.date.issued2014-05
dc.description.abstractThe somatic mutations in a cancer genome are the aggregate outcome of one or more mutational processes operative through the lifetime of the individual with cancer. Each mutational process leaves a characteristic mutational signature determined by the mechanisms of DNA damage and repair that constitute it. A role was recently proposed for the APOBEC family of cytidine deaminases in generating particular genome-wide mutational signatures and a signature of localized hypermutation called kataegis. A germline copy number polymorphism involving APOBEC3A and APOBEC3B, which effectively deletes APOBEC3B, has been associated with modestly increased risk of breast cancer. Here we show that breast cancers in carriers of the deletion show more mutations of the putative APOBEC-dependent genome-wide signatures than cancers in non-carriers. The results suggest that the APOBEC3A-APOBEC3B germline deletion allele confers cancer susceptibility through increased activity of APOBEC-dependent mutational processes, although the mechanism by which this increase in activity occurs remains unknown.
dc.description.sponsorshipWe would like to thank the Wellcome Trust for support (grant reference 098051). SN-Z is a Wellcome-Beit Prize Fellow and is supported through a Wellcome Trust Intermediate Fellowship (grant reference WT100183MA). PJC is personally funded through a Wellcome Trust Senior Clinical Research Fellowship (grant reference WT088340MA). NB is an EHA fellow and is supported by a Lady Tata Memorial Trust award. The H.L. Holmes Award from the National Research Council Canada and an EMBO Fellowship supports AS.
dc.identifier.doi10.17863/CAM.42271
dc.identifier.eissn1546-1718
dc.identifier.issn1061-4036
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/295210
dc.languageeng
dc.language.isoen
dc.publisherNature Publishing Group
dc.subjectBreast Neoplasms
dc.subjectCytidine Deaminase
dc.subjectDNA Copy Number Variations
dc.subjectFemale
dc.subjectGenetic Markers
dc.subjectGenetic Predisposition to Disease
dc.subjectHumans
dc.subjectMinor Histocompatibility Antigens
dc.subjectMutagenesis
dc.subjectProteins
dc.subjectSequence Deletion
dc.titleAssociation of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer.
dc.typeArticle
dcterms.dateAccepted2014-03-06
prism.endingPage491
prism.issueIdentifier5
prism.publicationDate2014
prism.publicationNameNat Genet
prism.startingPage487
prism.volume46
pubs.funder-project-idEuropean Commission (242006)
rioxxterms.licenseref.startdate2014-05
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1038/ng.2955
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