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dc.contributor.authorBrooks, Angela N.en_US
dc.contributor.authorChoi, Peter S.en_US
dc.contributor.authorde Waal, Lucen_US
dc.contributor.authorSharifnia, Tanazen_US
dc.contributor.authorImielinski, Marcinen_US
dc.contributor.authorSaksena, Gordonen_US
dc.contributor.authorPedamallu, Chandra Sekharen_US
dc.contributor.authorSivachenko, Andreyen_US
dc.contributor.authorRosenberg, Maraen_US
dc.contributor.authorChmielecki, Juliannen_US
dc.contributor.authorLawrence, Michael S.en_US
dc.contributor.authorDeLuca, David S.en_US
dc.contributor.authorGetz, Gaden_US
dc.contributor.authorMeyerson, Matthewen_US
dc.date.accessioned2014-03-11T13:54:00Z
dc.date.issued2014en_US
dc.identifier.citationBrooks, A. N., P. S. Choi, L. de Waal, T. Sharifnia, M. Imielinski, G. Saksena, C. S. Pedamallu, et al. 2014. “A Pan-Cancer Analysis of Transcriptome Changes Associated with Somatic Mutations in U2AF1 Reveals Commonly Altered Splicing Events.” PLoS ONE 9 (1): e87361. doi:10.1371/journal.pone.0087361. http://dx.doi.org/10.1371/journal.pone.0087361.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11879914
dc.description.abstractAlthough recurrent somatic mutations in the splicing factor U2AF1 (also known as U2AF35) have been identified in multiple cancer types, the effects of these mutations on the cancer transcriptome have yet to be fully elucidated. Here, we identified splicing alterations associated with U2AF1 mutations across distinct cancers using DNA and RNA sequencing data from The Cancer Genome Atlas (TCGA). Using RNA-Seq data from 182 lung adenocarcinomas and 167 acute myeloid leukemias (AML), in which U2AF1 is somatically mutated in 3–4% of cases, we identified 131 and 369 splicing alterations, respectively, that were significantly associated with U2AF1 mutation. Of these, 30 splicing alterations were statistically significant in both lung adenocarcinoma and AML, including three genes in the Cancer Gene Census, CTNNB1, CHCHD7, and PICALM. Cell line experiments expressing U2AF1 S34F in HeLa cells and in 293T cells provide further support that these altered splicing events are caused by U2AF1 mutation. Consistent with the function of U2AF1 in 3′ splice site recognition, we found that S34F/Y mutations cause preferences for CAG over UAG 3′ splice site sequences. This report demonstrates consistent effects of U2AF1 mutation on splicing in distinct cancer cell types.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0087361en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909098/pdf/en
dash.licenseLAAen_US
dc.subjectBiologyen
dc.subjectComputational Biologyen
dc.subjectGenomicsen
dc.subjectGenome Analysis Toolsen
dc.subjectTranscriptomesen
dc.subjectGeneticsen
dc.subjectCancer Geneticsen
dc.subjectGene Splicingen
dc.subjectMedicineen
dc.subjectHematologyen
dc.subjectHematologic Cancers and Related Disordersen
dc.subjectLeukemiasen
dc.subjectOncologyen
dc.subjectCancers and Neoplasmsen
dc.subjectLung and Intrathoracic Tumorsen
dc.subjectAdenocarcinoma of the Lungen
dc.subjectNon-Small Cell Lung Canceren
dc.subjectBasic Cancer Researchen
dc.titleA Pan-Cancer Analysis of Transcriptome Changes Associated with Somatic Mutations in U2AF1 Reveals Commonly Altered Splicing Eventsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorBrooks, Angela N.en_US
dc.date.available2014-03-11T13:54:00Z
dc.identifier.doi10.1371/journal.pone.0087361*
dash.authorsorderedfalse
dash.contributor.affiliatedChoi, Peter
dash.contributor.affiliatedBrooks, Angela
dash.contributor.affiliatedMeyerson, Matthew


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