Signatures of positive selection reveal a universal role of chromatin modifiers as cancer driver genes

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Zapata Ortiz, Luis, 1985-ca
• dc.contributor.author Sušak, Hana, 1985-ca
• dc.contributor.author Drechsel, Oliverca
• dc.contributor.author Friedländer, Marc R.ca
• dc.contributor.author Estivill, Xavier, 1955-ca
• dc.contributor.author Ossowski, Stephanca
• dc.date.accessioned 2018-07-18T07:59:00Z
• dc.date.available 2018-07-18T07:59:00Z
• dc.date.issued 2017
• dc.description.abstract Tumors are composed of an evolving population of cells subjected to tissue-specific selection, which fuels tumor heterogeneity and ultimately complicates cancer driver gene identification. Here, we integrate cancer cell fraction, population recurrence, and functional impact of somatic mutations as signatures of selection into a Bayesian model for driver prediction. We demonstrate that our model, cDriver, outperforms competing methods when analyzing solid tumors, hematological malignancies, and pan-cancer datasets. Applying cDriver to exome sequencing data of 21 cancer types from 6,870 individuals revealed 98 unreported tumor type-driver gene connections. These novel connections are highly enriched for chromatin-modifying proteins, hinting at a universal role of chromatin regulation in cancer etiology. Although infrequently mutated as single genes, we show that chromatin modifiers are altered in a large fraction of cancer patients. In summary, we demonstrate that integration of evolutionary signatures is key for identifying mutational driver genes, thereby facilitating the discovery of novel therapeutic targets for cancer treatment.
• dc.description.sponsorship We acknowledge support of the Spanish Ministry of Economy and Competitiveness, 'Centro de Excelencia Severo Ochoa 2013-2017'. We acknowledge the support of the CERCA Programme/Generalitat de Catalunya. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 635290. Luis Zapata has been supported by the International PhD scholarship program of La Caixa at CRG.
• dc.format.mimetype application/pdf
• dc.identifier.citation Zapata L, Susak H, Drechsel O, Friedländer MR, Estivill X, Ossowski S. Signatures of positive selection reveal a universal role of chromatin modifiers as cancer driver genes. Sci Rep. 2017 Oct 13;7(1):13124. DOI: 10.1038/s41598-017-12888-1
• dc.identifier.doi http://dx.doi.org/10.1038/s41598-017-12888-1
• dc.identifier.issn 2045-2322
• dc.identifier.uri http://hdl.handle.net/10230/35185
• dc.language.iso eng
• dc.publisher Nature Publishing Groupca
• dc.relation.ispartof Scientific Reports. 2017 Oct 13;7(1):13124
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/635290
• dc.rights © The Author(s) 2017. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Cancer genetics
• dc.subject.keyword Cancer genomics
• dc.subject.keyword Cell fraction
• dc.subject.keyword Computational models
• dc.title Signatures of positive selection reveal a universal role of chromatin modifiers as cancer driver genesca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion