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The genome as a record of environmental exposure.

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cam.issuedOnline2015-10-06
dc.contributor.authorNik-Zainal, Serena
dc.contributor.authorKucab, Jill E
dc.contributor.authorMorganella, Sandro
dc.contributor.authorGlodzik, Dominik
dc.contributor.authorAlexandrov, Ludmil B
dc.contributor.authorArlt, Volker M
dc.contributor.authorWeninger, Annette
dc.contributor.authorHollstein, Monica
dc.contributor.authorStratton, Michael R
dc.contributor.authorPhillips, David H
dc.contributor.orcidNik-Zainal Abidin, Serena [0000-0001-5054-1727]
dc.date.accessioned2018-09-10T22:16:42Z
dc.date.available2018-09-10T22:16:42Z
dc.date.issued2015-11
dc.description.abstractWhole genome sequencing of human tumours has revealed distinct patterns of mutation that hint at the causative origins of cancer. Experimental investigations of the mutations and mutation spectra induced by environmental mutagens have traditionally focused on single genes. With the advent of faster cheaper sequencing platforms, it is now possible to assess mutation spectra in experimental models across the whole genome. As a proof of principle, we have examined the whole genome mutation profiles of mouse embryo fibroblasts immortalised following exposure to benzo[a]pyrene (BaP), ultraviolet light (UV) and aristolochic acid (AA). The results reveal that each mutagen induces a characteristic mutation signature: predominantly G→T mutations for BaP, C→T and CC→TT for UV and A→T for AA. The data are not only consistent with existing knowledge but also provide additional information at higher levels of genomic organisation. The approach holds promise for identifying agents responsible for mutations in human tumours and for shedding light on the aetiology of human cancer.
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.27420
dc.identifier.eissn1464-3804
dc.identifier.issn0267-8357
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/280056
dc.languageeng
dc.language.isoeng
dc.publisherOxford University Press (OUP)
dc.publisher.urlhttp://dx.doi.org/10.1093/mutage/gev073
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAnimals
dc.subjectCell Line
dc.subjectCell Transformation, Neoplastic
dc.subjectDNA Mutational Analysis
dc.subjectDNA Replication
dc.subjectEnvironmental Exposure
dc.subjectFibroblasts
dc.subjectGenome
dc.subjectGenome-Wide Association Study
dc.subjectGenomics
dc.subjectHigh-Throughput Nucleotide Sequencing
dc.subjectHumans
dc.subjectMice
dc.subjectMutagenesis
dc.subjectMutagens
dc.subjectMutation
dc.subjectNeoplasms
dc.subjectTranscription, Genetic
dc.titleThe genome as a record of environmental exposure.
dc.typeArticle
prism.endingPage770
prism.issueIdentifier6
prism.publicationDate2015
prism.publicationNameMutagenesis
prism.startingPage763
prism.volume30
pubs.funder-project-idWellcome Trust (101126/Z/13/Z)
rioxxterms.licenseref.startdate2015-11
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1093/mutage/gev073

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