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dc.contributor.authorMartincorena, Iñigo
dc.contributor.authorFowler, Joanna C
dc.contributor.authorWabik, Agnieszka
dc.contributor.authorLawson, Andrew
dc.contributor.authorAbascal, Federico
dc.contributor.authorHall, Michael
dc.contributor.authorCagan, Alex
dc.contributor.authorMurai, Kasumi
dc.contributor.authorMahbubani, Krishnaa
dc.contributor.authorStratton, Michael R
dc.contributor.authorFitzgerald, Rebecca
dc.contributor.authorHandford, Penny A
dc.contributor.authorCampbell, Peter J
dc.contributor.authorSaeb-Parsy, Kourosh
dc.contributor.authorJones, Philip
dc.date.accessioned2018-12-07T00:30:50Z
dc.date.available2018-12-07T00:30:50Z
dc.date.issued2018-11-23
dc.identifier.issn0036-8075
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/286388
dc.description.abstractThe extent to which cells in normal tissues accumulate mutations throughout life is poorly understood. Some mutant cells expand into clones that can be detected by genome sequencing. We mapped mutant clones in normal esophageal epithelium from nine donors (age range, 20 to 75 years). Somatic mutations accumulated with age and were caused mainly by intrinsic mutational processes. We found strong positive selection of clones carrying mutations in 14 cancer genes, with tens to hundreds of clones per square centimeter. In middle-aged and elderly donors, clones with cancer-associated mutations covered much of the epithelium, with NOTCH1 and TP53 mutations affecting 12 to 80% and 2 to 37% of cells, respectively. Unexpectedly, the prevalence of NOTCH1 mutations in normal esophagus was several times higher than in esophageal cancers. These findings have implications for our understanding of cancer and aging.
dc.description.sponsorshipWellcome Trust Cancer Research UK
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherAmerican Association for the Advancement of Science (AAAS)
dc.subjectEsophagus
dc.subjectClone Cells
dc.subjectHumans
dc.subjectEsophageal Neoplasms
dc.subjectAging
dc.subjectMutation
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectTumor Suppressor Protein p53
dc.subjectReceptor, Notch1
dc.subjectYoung Adult
dc.subjectSelection, Genetic
dc.titleSomatic mutant clones colonize the human esophagus with age.
dc.typeArticle
prism.endingPage917
prism.issueIdentifier6417
prism.publicationDate2018
prism.publicationNameScience
prism.startingPage911
prism.volume362
dc.identifier.doi10.17863/CAM.31457
dcterms.dateAccepted2018-10-03
rioxxterms.versionofrecord10.1126/science.aau3879
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-11
dc.contributor.orcidMartincorena, Iñigo [0000-0003-1122-4416]
dc.contributor.orcidFowler, Joanna C [0000-0001-7546-369X]
dc.contributor.orcidWabik, Agnieszka [0000-0001-7231-2343]
dc.contributor.orcidLawson, Andrew [0000-0003-3592-1005]
dc.contributor.orcidAbascal, Federico [0000-0002-6201-1587]
dc.contributor.orcidHall, Michael [0000-0003-2904-6902]
dc.contributor.orcidMahbubani, Krishnaa [0000-0002-1327-2334]
dc.contributor.orcidStratton, Michael R [0000-0001-6035-153X]
dc.contributor.orcidFitzgerald, Rebecca [0000-0002-3434-3568]
dc.contributor.orcidHandford, Penny A [0000-0002-0590-7651]
dc.contributor.orcidSaeb-Parsy, Kourosh [0000-0002-0633-3696]
dc.contributor.orcidJones, Philip [0000-0002-5904-795X]
dc.identifier.eissn1095-9203
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMRC (unknown)
pubs.funder-project-idCancer Research UK (C609/A17257)
pubs.funder-project-idMedical Research Council (MC_UU_12022/3)
pubs.funder-project-idMedical Research Council (MC_UU_12022/2)
cam.issuedOnline2018-10-18
rioxxterms.freetoread.startdate2019-11-30


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