Altered oncomodules underlie chromatin regulatory factors driver mutations.
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- dc.contributor.author Frigola, Joanca
- dc.contributor.author Iturbide Martínez de Albéniz, Ane, 1989-ca
- dc.contributor.author López Bigas, Núriaca
- dc.contributor.author Peiró Sales, Sandraca
- dc.contributor.author González-Pérez, Abelca
- dc.date.accessioned 2016-10-10T10:46:02Z
- dc.date.available 2016-10-10T10:46:02Z
- dc.date.issued 2016
- dc.description.abstract Chromatin regulatory factors (CRFs), are known to be involved in tumorigenesis in several cancer types. Nevertheless, the molecular mechanisms through which driver alterations of CRFs cause tumorigenesis remain unknown. Here, we developed a CRFs Oncomodules Discovery approach, which mines several sources of cancer genomics and perturbaomics data. The approach prioritizes sets of genes significantly miss-regulated in primary tumors (oncomodules) bearing mutations of driver CRFs. We applied the approach to eleven TCGA tumor cohorts and uncovered oncomodules potentially associated to mutations of five driver CRFs in three cancer types. Our results revealed, for example, the potential involvement of the mTOR pathway in the development of tumors with loss-of-function mutations of MLL2 in head and neck squamous cell carcinomas. The experimental validation that MLL2 loss-of-function increases the sensitivity of cancer cell lines to mTOR inhibition lends further support to the validity of our approach. The potential oncogenic modules detected by our approach may guide experiments proposing ways to indirectly target driver mutations of CRFs.ca
- dc.description.sponsorship AGP is supported by a Ramon y Cajal grant (RYC-2013-14554), funded by the Spanish Ministry of Economy,/nwhich also supports the publication of this article.
- dc.format.mimetype application/pdfca
- dc.identifier.citation Frigola J, Iturbide A, Lopez-Bigas N, Peiro S, Gonzalez-Perez A. Altered oncomodules underlie chromatin regulatory factors driver mutations. Oncotarget. 2016 May 24;7(21):30748-59. DOI: 10.18632/oncotarget.8752ca
- dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.8752
- dc.identifier.issn 1949-2553
- dc.identifier.uri http://hdl.handle.net/10230/27395
- dc.language.iso engca
- dc.publisher Impact Journalsca
- dc.relation.ispartof Oncotarget. 2016 May 24;7(21):30748-59
- dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/RYC2013-14554
- dc.rights Copyright @ 2016 Impact Journals, LLC. All site content, except where otherwise noted, is licensed under a https://creativecommons.org/licenses/by/3.0/ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri https://creativecommons.org/licenses/by/3.0/ca
- dc.subject.other Oncologiaca
- dc.subject.other Càncerca
- dc.subject.other Genèticaca
- dc.title Altered oncomodules underlie chromatin regulatory factors driver mutations.ca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca