Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines

DC FieldValueLanguage
dc.contributor.authorCampbell, James-
dc.contributor.authorRyan, Colm J.-
dc.contributor.authorBrough, Rachel-
dc.contributor.authoret al.-
dc.date.accessioned2019-04-02T08:13:50Z-
dc.date.available2019-04-02T08:13:50Z-
dc.date.copyright2016 Elsevieren_US
dc.date.issued2016-03-15-
dc.identifier.citationCell Reportsen_US
dc.identifier.urihttp://hdl.handle.net/10197/9764-
dc.description.abstractOne approach to identifying cancer-specific vulnerabilities and therapeutic targets is to profile genetic dependencies in cancer cell lines. Here, we describe data from a series of siRNA screens that identify the kinase genetic dependencies in 117 cancer cell lines from ten cancer types. By integrating the siRNA screen data with molecular profiling data, including exome sequencing data, we show how vulnerabilities/genetic dependencies that are associated with mutations in specific cancer driver genes can be identified. By integrating additional data sets into this analysis, including protein-protein interaction data, we also demonstrate that the genetic dependencies associated with many cancer driver genes form dense connections on functional interaction networks. We demonstrate the utility of this resource by using it to predict the drug sensitivity of genetically or histologically defined subsets of tumor cell lines, including an increased sensitivity of osteosarcoma cell lines to FGFR inhibitors and SMAD4 mutant tumor cells to mitotic inhibitors.en_US
dc.description.sponsorshipEuropean Commission - Seventh Framework Programme (FP7)en_US
dc.description.sponsorshipHealth Research Boarden_US
dc.description.sponsorshipScience Foundation Irelanden_US
dc.description.sponsorshipWellcome Trusten_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.rightsThis is the author’s version of a work that was accepted for publication in Cell Reports. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cell Reports (14, 10, (DATE)) DOI:10.1016/j.celrep.2016.02.023en_US
dc.subjectCancer cell linesen_US
dc.subjectIntegrating genotype dataen_US
dc.subjectKinase dependenciesen_US
dc.subjectProtein interaction dataen_US
dc.subjectGenetic dependenciesen_US
dc.subjectMutant cell linesen_US
dc.subjectKinome siRNA screeningen_US
dc.titleLarge-Scale Profiling of Kinase Dependencies in Cancer Cell Linesen_US
dc.typeJournal Articleen_US
dc.statusPeer revieweden_US
dc.identifier.volume14en_US
dc.identifier.issue10en_US
dc.identifier.startpage2490en_US
dc.identifier.endpage2501en_US
dc.identifier.doi10.1016/j.celrep.2016.02.023-
dc.neeo.contributorCampbell|James|aut|-
dc.neeo.contributorRyan|Colm J.|aut|-
dc.neeo.contributorBrough|Rachel|aut|-
dc.neeo.contributoret al.||aut|-
dc.description.othersponsorshipCancer Research UKen_US
dc.description.othersponsorshipBreast Cancer Nowen_US
dc.description.othersponsorshipNational Health Serviceen_US
dc.date.updated2017-12-06-
dc.identifier.grantidC347/A8363-
dc.identifier.grantid260791-
dc.identifier.grantid103049/Z/13/Z-
item.fulltextWith Fulltext-
item.grantfulltextopen-
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