Cancer type-dependent genetic interactions between cancer driver alterations indicate plasticity of epistasis across cell types

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  • dc.contributor.author Park, Solipca
  • dc.contributor.author Lehner, Ben, 1978-ca
  • dc.date.accessioned 2015-11-16T14:48:16Z
  • dc.date.available 2015-11-16T14:48:16Z
  • dc.date.issued 2015
  • dc.description.abstract Cancers, like many diseases, are normally caused by combinations of genetic alterations rather than by changes affecting single genes. It is well established that the genetic alterations that drive cancer often interact epistatically, having greater or weaker consequences in combination than expected from their individual effects. In a stringent statistical analysis of data from > 3,000 tumors, we find that the co-occurrence and mutual exclusivity relationships between cancer driver alterations change quite extensively in different types of cancer. This cannot be accounted for by variation in tumor heterogeneity or unrecognized cancer subtypes. Rather, it suggests that how genomic alterations interact cooperatively or partially redundantly to driver cancer changes in different types of cancers. This re-wiring of epistasis across cell types is likely to be a basic feature of genetic architecture, with important implications for understanding the evolution of multicellularity and human genetic diseases. In addition, if this plasticity of epistasis across cell types is also true for synthetic lethal interactions, a synthetic lethal strategy to kill cancer cells may frequently work in one type of cancer but prove ineffective in another.en
  • dc.description.sponsorship S.P. was funded by a Postdoctoral Fellowship from Novartis and by the Juan de la Cierva program (MINECO). Work in the laboratory of B.L. is funded by a European Research Council (ERC) Consolidator Grant (IR-DC, GA616434), Plan Nacional Grant BFU2011-26206 (MINECO), AGAUR (2009 SGR 112), the EMBO Young Investigator Program (MINECO), EU Framework 7 project 277899 4DCellFate, the EMBLCRG Systems Biology Program, the Severo Ochoa Program, and the AXA Research Fund.en
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Park S, Lehner B. Cancer type-dependent genetic interactions between cancer driver alterations indicate plasticity of epistasis across cell types. Molecular systems biology. 2015;11(7):824. DOI: 10.15252/msb.20156102en
  • dc.identifier.doi http://dx.doi.org/10.15252/msb.20156102
  • dc.identifier.issn 1744-4292
  • dc.identifier.uri http://hdl.handle.net/10230/25106
  • dc.language.iso engca
  • dc.publisher Wiley Blackwellca
  • dc.relation.ispartof Molecular systems biology. 2015;11(7):824
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/616434
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/277899
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011-26206
  • dc.rights © 2015 The Authors. Published under the terms of the CC BY 4.0 license. This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/ca
  • dc.subject.keyword Cancer
  • dc.subject.keyword Epistasis
  • dc.subject.keyword Evolution
  • dc.subject.keyword Genetic interaction networks
  • dc.subject.keyword Tissue specificity
  • dc.subject.other Genètica molecularca
  • dc.subject.other Càncerca
  • dc.title Cancer type-dependent genetic interactions between cancer driver alterations indicate plasticity of epistasis across cell typesen
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca