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dc.contributor.authorAlexandrov, Ludmil B
dc.contributor.authorNik-Zainal Abidin, Serena
dc.contributor.authorSiu, Hoi Cheong
dc.contributor.authorLeung, Suet Yi
dc.contributor.authorStratton, Michael R
dc.date.accessioned2018-11-01T14:02:44Z
dc.date.available2018-11-01T14:02:44Z
dc.date.issued2015-10-29
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/284499
dc.description.abstractTargeting defects in the DNA repair machinery of neoplastic cells, for example, those due to inactivating BRCA1 and/or BRCA2 mutations, has been used for developing new therapies in certain types of breast, ovarian and pancreatic cancers. Recently, a mutational signature was associated with failure of double-strand DNA break repair by homologous recombination based on its high mutational burden in samples harbouring BRCA1 or BRCA2 mutations. In pancreatic cancer, all responders to platinum therapy exhibit this mutational signature including a sample that lacked any defects in BRCA1 or BRCA2. Here, we examine 10,250 cancer genomes across 36 types of cancer and demonstrate that, in addition to breast, ovarian and pancreatic cancers, gastric cancer is another cancer type that exhibits this mutational signature. Our results suggest that 7-12% of gastric cancers have defective double-strand DNA break repair by homologous recombination and may benefit from either platinum therapy or PARP inhibitors.
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.subjectHumans
dc.subjectNeoplasms
dc.subjectBreast Neoplasms
dc.subjectStomach Neoplasms
dc.subjectPancreatic Neoplasms
dc.subjectBRCA1 Protein
dc.subjectBRCA2 Protein
dc.subjectDNA Repair
dc.subjectMutation
dc.subjectFemale
dc.subjectMale
dc.subjectDNA Breaks
dc.titleA mutational signature in gastric cancer suggests therapeutic strategies.
dc.typeArticle
prism.publicationDate2015
prism.publicationNameNat Commun
prism.startingPage8683
prism.volume6
dc.identifier.doi10.17863/CAM.31874
dcterms.dateAccepted2015-09-18
rioxxterms.versionofrecord10.1038/ncomms9683
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2015-10-29
dc.contributor.orcidAlexandrov, Ludmil B [0000-0003-3596-4515]
dc.contributor.orcidNik-Zainal Abidin, Serena [0000-0001-5054-1727]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Review
cam.issuedOnline2015-10-29


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