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Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma

2015Journal article Open access
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dc.contributor.authorGrosso, Ana Rita
dc.contributor.authorLeite, Ana Paula
dc.contributor.authorCarvalho, Silvia
dc.contributor.authorRamos De Matos, Mafalda
dc.contributor.authorMartins, Filipa B.
dc.contributor.authorVítor, Alexandra
dc.contributor.authorDesterro, Joana
dc.contributor.authorCarmo-Fonseca, Maria
dc.contributor.authorde Almeida, Sérgio F.
dc.date.accessioned2022-02-04T15:21:41Z
dc.date.available2022-02-04T15:21:41Z
dc.date.issued2015
dc.description© 2015, Grosso et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.pt_PT
dc.description.abstractAberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Genome Atlas (TCGA) reveals that transcription read-through beyond the termination site is a source of transcriptome diversity in cancer cells. Amongst the genes most frequently mutated in ccRCC, we identified SETD2 inactivation as a potent enhancer of transcription read-through. We further show that invasion of neighbouring genes and generation of RNA chimeras are functional outcomes of transcription read-through. We identified the BCL2 oncogene as one of such invaded genes and detected a novel chimera, the CTSC-RAB38, in 20% of ccRCC samples. Collectively, our data highlight a novel link between transcription read-through and aberrant expression of oncogenes and chimeric transcripts that is prevalent in cancer.pt_PT
dc.description.sponsorshipThis work was supported by Fundação para a Ciência e Tecnologia (FCT), Portugal (PTDC/BIM-ONC/0384-2012 to SFdA). MRM is a FCT PhD fellow (SFRH/BD/92208/2013). ACV is a Lisbon BioMed PhD fellow funded by FCT (SFRH/BD/52232/2013). ARG is the recipient of a FCT Investigator award (IF/00510/2014).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationElife. 2015 Nov 17;4:e09214.pt_PT
dc.identifier.doi10.7554/eLife.09214pt_PT
dc.identifier.eissn2050-084X
dc.identifier.urihttp://hdl.handle.net/10451/51125
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publishereLifept_PT
dc.relationPTDC/BIM-ONC/0384-2012pt_PT
dc.relationNOVEL MECHANISMS OFGENOMIC AND EPIGENOMIC STABILITY
dc.relationIF/00510/2014pt_PT
dc.relation.publisherversionhttps://elifesciences.org/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectBCL2 oncogenept_PT
dc.subjectRNA chimeraspt_PT
dc.subjectCancer genespt_PT
dc.subjectChromosomespt_PT
dc.subjectClear cell renal cell carcinomapt_PT
dc.subjectGenespt_PT
dc.subjectHumanpt_PT
dc.subjectHuman biologypt_PT
dc.subjectMedicinept_PT
dc.subjectTranscription read-throughpt_PT
dc.titlePervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinomapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleNOVEL MECHANISMS OFGENOMIC AND EPIGENOMIC STABILITY
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F92208%2F2013/PT
oaire.citation.titleeLifept_PT
oaire.citation.volume4pt_PT
oaire.fundingStreamOE
person.familyNameGrosso
person.familyNameLeite
person.familyNameCarvalho
person.familyNameRamos de Matos
person.familyNameVítor
person.familyNamePinto Desterro
person.familyNameCarmo-Fonseca
person.familyNameFERNANDES DE ALMEIDA
person.givenNameAna Rita
person.givenNameAna Paula
person.givenNameSilvia
person.givenNameMafalda
person.givenNameAlexandra
person.givenNameMaria Joana
person.givenNameMaria
person.givenNameSÉRGIO ALEXANDRE
person.identifierI-6656-2013
person.identifier.ciencia-id3D18-571E-133A
person.identifier.ciencia-id8F13-7782-254E
person.identifier.ciencia-id9E11-7F4C-67F4
person.identifier.ciencia-idB31F-0435-0753
person.identifier.ciencia-id7D18-F40F-7CC1
person.identifier.orcid0000-0001-6974-4209
person.identifier.orcid0000-0001-5773-3211
person.identifier.orcid0000-0001-6436-205X
person.identifier.orcid0000-0002-4206-2854
person.identifier.orcid0000-0002-6178-3980
person.identifier.orcid0000-0002-6359-7233
person.identifier.orcid0000-0002-3402-7143
person.identifier.orcid0000-0002-7774-1355
person.identifier.scopus-author-id26639262500
person.identifier.scopus-author-id35167917000
person.identifier.scopus-author-id6602949583
person.identifier.scopus-author-id7007128195
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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