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dc.contributor.authorPark, Solip
dc.contributor.authorSupek, Fran
dc.contributor.authorLehner, Ben
dc.date.accessioned2022-03-07T09:47:53Z
dc.date.available2022-03-07T09:47:53Z
dc.date.issued2021-12-03
dc.identifier.citationNat Commun . 2021;12(1):7051.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/13729
dc.descriptionWe thank Luis Garcia-Jimeno for assistance with permutation. S.P. is supported by the Agencia Estatal de Investigacion, Ministerio de Ciencia e Innovacion (MCIN/AEI/10.13039/501100011033) through the RETOS project PID2019-109571RA-I00. This work was funded by the European Research Council (ERC) Starting grant (HYPER-INSIGHT, 757700) to F.S. and ERC Consolidator (IR-DC, 616434) and Advanced (MUTANOMICS, 883742) grants to B.L. F.S. and B.L. are funded by the ICREA Research Professor program. S.P., F.S., and B.L. acknowledge the support of the Severo Ochoa Centres of Excellence program to the CNIO, IRB Barcelona, and to the CRG (MCIN/AEI/10.13039/50110001103), respectively. B.L. and F.S. Work is funded with the grants BFU2017-89488-P and RegioMut BFU2017-89833-P (MCIN/AEI/10.13039/501100011033/FEDER "A way to make Europe"), respectively. B.L. is further supported by the Bettencourt Schueller Foundation, the Agencia de Gestio d'Ajuts Universitaris i de Recerca (2017 SGR 1322), and the Centres de Recerca de Catalunya (CERCA) program/Generalitat de Catalunya. B.L. also acknowledges the support of the Spanish Ministry of Economy, Industry, and Competitiveness to the European Molecular Biology Laboratory (EMBL) partnership. The results shown here are in whole or part based upon data generated by the TCGA Research Network.es_ES
dc.description.abstractThe classic two-hit model posits that both alleles of a tumor suppressor gene (TSG) must be inactivated to cause cancer. In contrast, for some oncogenes and haploinsufficient TSGs, a single genetic alteration can suffice to increase tumor fitness. Here, by quantifying the interactions between mutations and copy number alterations (CNAs) across 10,000 tumors, we show that many cancer genes actually switch between acting as one-hit or two-hit drivers. Third order genetic interactions identify the causes of some of these switches in dominance and dosage sensitivity as mutations in other genes in the same biological pathway. The correct genetic model for a gene thus depends on the other mutations in a genome, with a second hit in the same gene or an alteration in a different gene in the same pathway sometimes representing alternative evolutionary paths to cancer.es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Group es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectMUTATIONSes_ES
dc.subjectLANDSCAPEes_ES
dc.subjectPATHWAYSes_ES
dc.subjectPATTERNSes_ES
dc.subject.meshGenes, Tumor Suppressor es_ES
dc.subject.meshModels, Genetices_ES
dc.subject.meshOncogenes es_ES
dc.subject.meshAlleles es_ES
dc.subject.meshCarcinogenesis es_ES
dc.subject.meshDNA Copy Number Variations es_ES
dc.subject.meshDatasets as Topic es_ES
dc.subject.meshHaploinsufficiency es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMutation es_ES
dc.subject.meshNeoplasms es_ES
dc.titleHigher order genetic interactions switch cancer genes from two-hit to one-hit drivers.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID34862370es_ES
dc.format.volume12es_ES
dc.format.number1es_ES
dc.format.page7051es_ES
dc.identifier.doi10.1038/s41467-021-27242-3es_ES
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC) es_ES
dc.contributor.funderMinisterio de Ciencia e Innovación (España) es_ES
dc.contributor.funderUnión Europea. Comisión Europea es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn2041-1723es_ES
dc.relation.publisherversionhttps://doi.org/ 10.1038/s41467-021-27242-3.es_ES
dc.identifier.journalNature communicationses_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Biología Computacional Estructurales_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/757700es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/616434es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/883742es_ES
dc.rights.accessRightsopen accesses_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/BFU2017-89488-Pes_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/BFU2017-89833-Pes_ES


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