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dc.contributor.authorNik-Zainal Abidin, Serenaen
dc.contributor.authorWedge, David Cen
dc.contributor.authorAlexandrov, Ludmil Ben
dc.contributor.authorPetljak, Miaen
dc.contributor.authorButler, Adam Pen
dc.contributor.authorBolli, Niccoloen
dc.contributor.authorDavies, Helenen
dc.contributor.authorKnappskog, Stianen
dc.contributor.authorMartin, Sanchaen
dc.contributor.authorPapaemmanuil, Ellien
dc.contributor.authorRamakrishna, Manasaen
dc.contributor.authorShlien, Adamen
dc.contributor.authorSimonic, Ingriden
dc.contributor.authorXue, Yalien
dc.contributor.authorTyler-Smith, Chrisen
dc.contributor.authorCampbell, Peter Jen
dc.contributor.authorStratton, Michael Ren
dc.date.accessioned2019-08-02T11:13:14Z
dc.date.available2019-08-02T11:13:14Z
dc.date.issued2014-05en
dc.identifier.issn1061-4036
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/295210
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.languageengen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.subjectBreast Neoplasmsen
dc.subjectCytidine Deaminaseen
dc.subjectDNA Copy Number Variationsen
dc.subjectFemaleen
dc.subjectGenetic Markersen
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectHumansen
dc.subjectMinor Histocompatibility Antigensen
dc.subjectMutagenesisen
dc.subjectProteinsen
dc.subjectSequence Deletionen
dc.titleAssociation of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer.en
dc.typeArticle
prism.endingPage491
prism.issueIdentifier5en
prism.publicationDate2014en
prism.publicationNameNat Geneten
prism.startingPage487
prism.volume46en
dc.identifier.doi10.17863/CAM.42271
dcterms.dateAccepted2014-03-06en
rioxxterms.versionofrecord10.1038/ng.2955en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2014-05en
dc.contributor.orcidNik-Zainal Abidin, Serena [0000-0001-5054-1727]
dc.identifier.eissn1546-1718
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEC FP7 CP (242006)


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