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dc.contributor.authorRheinbay, Esther
dc.contributor.authorNielsen, Morten Muhlig
dc.contributor.authorAbascal, Federico
dc.contributor.authorWala, Jeremiah A
dc.contributor.authorShapira, Ofer
dc.contributor.authorTiao, Grace
dc.contributor.authorHornshøj, Henrik
dc.contributor.authorHess, Julian M
dc.contributor.authorJuul, Randi Istrup
dc.contributor.authorLin, Ziao
dc.contributor.authorFeuerbach, Lars
dc.contributor.authorSabarinathan, Radhakrishnan
dc.contributor.authorMadsen, Tobias
dc.contributor.authorKim, Jaegil
dc.contributor.authorMularoni, Loris
dc.contributor.authorShuai, Shimin
dc.contributor.authorLanzós, Andrés
dc.contributor.authorHerrmann, Carl
dc.contributor.authorMaruvka, Yosef E
dc.contributor.authorShen, Ciyue
dc.contributor.authorAmin, Samirkumar B
dc.contributor.authorBandopadhayay, Pratiti
dc.contributor.authorBertl, Johanna
dc.contributor.authorBoroevich, Keith A
dc.contributor.authorBusanovich, John
dc.contributor.authorCarlevaro-Fita, Joana
dc.contributor.authorChakravarty, Dimple
dc.contributor.authorChan, Calvin Wing Yiu
dc.contributor.authorCraft, David
dc.contributor.authorDhingra, Priyanka
dc.contributor.authorDiamanti, Klev
dc.contributor.authorFonseca, Nuno A
dc.contributor.authorGonzalez-Perez, Abel
dc.contributor.authorGuo, Qianyun
dc.contributor.authorHamilton, Mark P
dc.contributor.authorHaradhvala, Nicholas J
dc.contributor.authorHong, Chen
dc.contributor.authorIsaev, Keren
dc.contributor.authorJohnson, Todd A
dc.contributor.authorJuul, Malene
dc.contributor.authorKahles, Andre
dc.contributor.authorKahraman, Abdullah
dc.contributor.authorKim, Youngwook
dc.contributor.authorKomorowski, Jan
dc.contributor.authorKumar, Kiran
dc.contributor.authorKumar, Sushant
dc.contributor.authorLee, Donghoon
dc.contributor.authorLehmann, Kjong-Van
dc.contributor.authorLi, Yilong
dc.contributor.authorLiu, Eric Minwei
dc.contributor.authorLochovsky, Lucas
dc.contributor.authorPark, Keunchil
dc.contributor.authorPich, Oriol
dc.contributor.authorRoberts, Nicola D
dc.contributor.authorSaksena, Gordon
dc.contributor.authorSchumacher, Steven E
dc.contributor.authorSidiropoulos, Nikos
dc.contributor.authorSieverling, Lina
dc.contributor.authorSinnott-Armstrong, Nasa
dc.contributor.authorStewart, Chip
dc.contributor.authorTamborero, David
dc.contributor.authorTubio, Jose MC
dc.contributor.authorUmer, Husen M
dc.contributor.authorUusküla-Reimand, Liis
dc.contributor.authorWadelius, Claes
dc.contributor.authorWadi, Lina
dc.contributor.authorYao, Xiaotong
dc.contributor.authorZhang, Cheng-Zhong
dc.contributor.authorZhang, Jing
dc.contributor.authorHaber, James E
dc.contributor.authorHobolth, Asger
dc.contributor.authorImielinski, Marcin
dc.contributor.authorKellis, Manolis
dc.contributor.authorLawrence, Michael S
dc.contributor.authorvon Mering, Christian
dc.contributor.authorNakagawa, Hidewaki
dc.contributor.authorRaphael, Benjamin J
dc.contributor.authorRubin, Mark A
dc.contributor.authorSander, Chris
dc.contributor.authorStein, Lincoln D
dc.contributor.authorStuart, Joshua M
dc.contributor.authorTsunoda, Tatsuhiko
dc.contributor.authorWheeler, David A
dc.contributor.authorJohnson, Rory
dc.contributor.authorReimand, Jüri
dc.contributor.authorGerstein, Mark
dc.contributor.authorKhurana, Ekta
dc.contributor.authorCampbell, Peter J
dc.contributor.authorLópez-Bigas, Núria
dc.contributor.authorPCAWG Drivers and Functional Interpretation Working Group
dc.contributor.authorPCAWG Structural Variation Working Group
dc.contributor.authorWeischenfeldt, Joachim
dc.contributor.authorBeroukhim, Rameen
dc.contributor.authorMartincorena, Iñigo
dc.contributor.authorPedersen, Jakob Skou
dc.contributor.authorGetz, Gad
dc.contributor.authorPCAWG Consortium
dc.date.accessioned2021-02-04T16:23:46Z
dc.date.available2021-02-04T16:23:46Z
dc.date.issued2020-02
dc.date.submitted2018-01-19
dc.identifier.issn0028-0836
dc.identifier.others41586-020-1965-x
dc.identifier.other1965
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/317140
dc.description.abstractThe discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectArticle
dc.subject/631/67/69
dc.subject/631/114
dc.subject/45/23
dc.subjectarticle
dc.titleAnalyses of non-coding somatic drivers in 2,658 cancer whole genomes.
dc.typeArticle
dc.date.updated2021-02-04T16:23:45Z
prism.endingPage111
prism.issueIdentifier7793
prism.publicationNameNature
prism.startingPage102
prism.volume578
dc.identifier.doi10.17863/CAM.64251
dcterms.dateAccepted2019-12-02
rioxxterms.versionofrecord10.1038/s41586-020-1965-x
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.identifier.eissn1476-4687
cam.issuedOnline2020-02-05


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)