Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes

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• dc.contributor.author Leiserson, Mark D.M.
• dc.contributor.author Vandin, Fabio
• dc.contributor.author Wu, Hsin-Ta
• dc.contributor.author Dobson, Jason R.
• dc.contributor.author Eldridge, Jonathan V.
• dc.contributor.author Thomas, Jacob L.
• dc.contributor.author Papoutsaki, Alexandra
• dc.contributor.author Kim, Younhun
• dc.contributor.author Niu, Beifang
• dc.contributor.author McLellan, Michael
• dc.contributor.author Lawrence, Michael S.
• dc.contributor.author Gonzalez-Perez, Abel
• dc.contributor.author Tamborero Noguera, David
• dc.contributor.author Cheng, Yuwei
• dc.contributor.author Ryslik, Gregory A.
• dc.contributor.author López Bigas, Núria
• dc.contributor.author Getz, Gad
• dc.contributor.author Ding, Li
• dc.contributor.author Raphael, Benjamin J.
• dc.date.accessioned 2019-01-21T08:49:26Z
• dc.date.available 2019-01-21T08:49:26Z
• dc.date.issued 2015
• dc.description.abstract Cancers exhibit extensive mutational heterogeneity, and the resulting long-tail phenomenon complicates the discovery of genes and pathways that are significantly mutated in cancer. We perform a pan-cancer analysis of mutated networks in 3,281 samples from 12 cancer types from The Cancer Genome Atlas (TCGA) using HotNet2, a new algorithm to find mutated subnetworks that overcomes the limitations of existing single-gene, pathway and network approaches. We identify 16 significantly mutated subnetworks that comprise well-known cancer signaling pathways as well as subnetworks with less characterized roles in cancer, including cohesin, condensin and others. Many of these subnetworks exhibit co-occurring mutations across samples. These subnetworks contain dozens of genes with rare somatic mutations across multiple cancers; many of these genes have additional evidence supporting a role in cancer. By illuminating these rare combinations of mutations, pan-cancer network analyses provide a roadmap to investigate new diagnostic and therapeutic opportunities across cancer types.
• dc.description.sponsorship This work is supported by US National Science Foundation (NSF) grant IIS-1016648 and US National Institutes of Health (NIH) grants R01HG005690, R01HG007069 and R01CA180776 to B.J.R. and by National Human Genome Research Institute (NHGRI) grant U01HG006517 to L.D. B.J.R. is supported by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund, an Alfred P. Sloan Research Fellowship and an NSF CAREER Award (CCF-1053753). M.D.M.L. is supported by NSF fellowship GRFP DGE 0228243
• dc.format.mimetype application/pdf
• dc.identifier.citation Leiserson MD, Vandin F, Wu HT, Dobson JR, Eldridge JV, Thomas JL et al. Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes. Nat Genet. 2015 Feb;47(2):106-14. DOI: 10.1038/ng.3168
• dc.identifier.doi http://dx.doi.org/10.1038/ng.3168
• dc.identifier.issn 1061-4036
• dc.identifier.uri http://hdl.handle.net/10230/36340
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nature Genetics. 2015 Feb;47(2):106-14
• dc.rights © Springer Nature Publishing AG. Leiserson MD, Vandin F, Wu HT, Dobson JR, Eldridge JV, Thomas JL et al. Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes. Nat Genet. 2015 Feb; 47(2): 106-14. http://dx.doi.org/10.1038/ng.3168
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Algorismes
• dc.subject.other Biologia computacional
• dc.subject.other Genòmica
• dc.subject.other Genètica
• dc.subject.other Tumors
• dc.subject.other Transducció de senyal cel·lular
• dc.title Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion