Leiserson, Mark D.M.Vandin, FabioWu, Hsin-TaDobson, Jason R.Eldridge, Jonathan V.Thomas, Jacob L.Papoutsaki, AlexandraKim, YounhunNiu, BeifangMcLellan, MichaelLawrence, Michael S.Gonzalez-Perez, AbelTamborero Noguera, DavidCheng, YuweiRyslik, Gregory A.López Bigas, NúriaGetz, GadDing, LiRaphael, Benjamin J.2019-01-212019-01-212015Leiserson 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.31681061-4036http://hdl.handle.net/10230/36340Cancers 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.application/pdfeng© 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.3168AlgorismesBiologia computacionalGenòmicaGenèticaTumorsTransducció de senyal cel·lularinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/ng.3168info:eu-repo/semantics/openAccess