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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes

674Citations signalées — pas une note de qualité
379Institutions déclarées
33Pays d’affiliation déclarés

Résumé fourni par la source

Abstract The discovery of drivers of cancer has traditionally focused on protein-coding genes 1–4 . 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) Consortium 5 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 drivers 6,7 , 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.

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Contrôle bibliographique ouvert

DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.

Titre Crossref
Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
Date Crossref
05/02/2020
Éditeur
Springer Science and Business Media LLC
Type
journal-article

Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude et ne compte pas comme une seconde source scientifique indépendante.

Institutions déclarées

Broad InstituteHarvard UniversityMassachusetts General HospitalCenter for Cancer ResearchAarhus University HospitalWellcome Sanger InstituteDana-Farber Cancer InstituteHarvard University PressGerman Cancer Research CenterHeidelberg UniversityUniversitat Pompeu FabraInstitute for Research in BiomedicineOntario Institute for Cancer ResearchUniversity of BernUniversity Hospital of BernThe University of Texas MD Anderson Cancer CenterBaylor College of MedicineRIKEN Center for Integrative Medical SciencesIcahn School of Medicine at Mount SinaiCornell UniversityWeill Cornell MedicineUppsala UniversityScience for Life LaboratoryEuropean Bioinformatics InstituteAarhus UniversityUniversity of TorontoMemorial Sloan Kettering Cancer CenterSIB Swiss Institute of BioinformaticsUniversity of ZurichSamsung Medical CenterSungkyunkwan UniversityInstitute of Computer SciencePolish Academy of SciencesYale UniversityUniversity of CambridgePlatelet BioGenesis (United States)University of CopenhagenRigshospitaletStanford UniversityUniversidade de Santiago de CompostelaCenter for Research in Molecular Medicine and Chronic DiseasesUniversidade de VigoKarolinska InstitutetTallinn University of TechnologySickKids FoundationNew York Genome CenterBrandeis UniversityMIT Computer Science and Artificial Intelligence LaboratoryPrinceton UniversityUniversity of California, Santa CruzTokyo Medical and Dental UniversityThe University of TokyoInstitució Catalana de Recerca i Estudis AvançatsTechnical University of DenmarkKorea Advanced Institute of Science and TechnologyBarcelona Supercomputing CenterUniversitat Politècnica de CatalunyaUniversity of Milano-BicoccaPeter MacCallum Cancer CentreCentre for Genomic RegulationSimon Fraser UniversityNational Cancer CenterUniversity of GothenburgGhent UniversitySangmyung UniversitySpanish National Cancer Research CentreThe University of MelbourneJames S. McDonnell FoundationEuropean Molecular Biology LaboratoryCopenhagen University HospitalOregon Health & Science UniversityChinese University of Hong KongXi'an Jiaotong UniversityThe University of Texas Health Science Center at HoustonNorthwestern UniversityNational Center for Tumor DiseasesJohns Hopkins UniversityJohns Hopkins MedicineUniversity of OttawaCancer Research UKBar-Ilan UniversityNational Institute of Environmental Health SciencesHopp Children's Cancer Center HeidelbergSkolkovo Institute of Science and TechnologySeoul National University HospitalBoston Children's HospitalQIMR Berghofer Medical Research InstituteWashington State UniversityBeth Israel Deaconess Medical CenterCancer Research InstituteUniversity of ChicagoUniversity of HelsinkiKeimyung University Dongsan Medical CenterKeimyung UniversityGachon University Gil Medical CenterHiroshima UniversityKing Faisal Specialist Hospital & Research CentreUniversität HamburgUniversity Medical Center Hamburg-EppendorfCanada's Michael Smith Genome Sciences CentreRoyal National Orthopaedic HospitalUniversity College LondonChristian-Albrechts-Universität zu KielThe University of QueenslandSalford Royal NHS Foundation TrustTokyo Women's Medical UniversityMolecular Oncology (United States)Los Alamos National LaboratoryUniversity Health NetworkToronto General HospitalEpigenomics (Germany)Universität UlmUniversity of North Carolina at Chapel HillOslo University HospitalConsorci Institut D'Investigacions Biomediques August Pi I SunyerUniversitat de BarcelonaUniversity of GlasgowUniversity of LeedsSt James's University HospitalPrincess Alexandra HospitalCase Western Reserve UniversityGloucestershire Royal HospitalUniversity of CalgaryInstitute of Cancer ResearchSidney Kimmel Comprehensive Cancer CenterRoyal Stoke University HospitalLa Trobe UniversityOlivia Newton-John Cancer Wellness & Research CentreOlivia Newton-John Cancer Research InstituteChinese Academy of SciencesComputer Network Information CenterGenome CanadaBuck Institute for Research on AgingDuke Medical CenterMedizinische Hochschule HannoverUniversity of California San DiegoCedars-Sinai Medical CenterQueen Mary University of LondonLeipzig UniversityUniversity of Southern CaliforniaSecretaria de SaludBerlin Institute of Health at Charité - Universitätsmedizin BerlinDuke University HospitalNational Institute of Biomedical GenomicsInstitute of Cancer ResearchDuke-NUS Medical SchoolLund UniversityHeinrich Heine University DüsseldorfFriedrich-Ebert-KrankenhausUniversity of OxfordMcGill UniversityUniversity of California, Los AngelesTampere University HospitalTampere UniversityCentre Léon BérardFox Chase Cancer CenterCentre international de recherche sur le cancerEarlham InstituteRadboud University NijmegenRadboud University Medical CenterRadboud Institute for Molecular Life SciencesBrigham and Women's HospitalThe Netherlands Cancer InstituteOncode InstituteBundesministerium für Forschung, Technologie und RaumfahrtThe University of SydneyMelanoma Institute AustraliaUniversity Hospital MünsterUniversity of California, San FranciscoNational Institutes of HealthNational Cancer InstituteRoyal Marsden NHS Foundation TrustInstitut Gustave RoussyUniversity of MichiganMichigan Center for Translational PathologyUniversity of PaviaUniversity of Alabama at BirminghamUniversity of TasmaniaMayo Clinic in ArizonaGarvan Institute of Medical ResearchUNSW SydneyMayo ClinicWinnMedWestmead Institute for Medical ResearchElectronics and Telecommunications Research InstituteInstitut National du CancerNational Cancer Centre SingaporeUniversity Hospital Schleswig-HolsteinUniversity of LübeckUniversity of AucklandVictorian Institute of Forensic MedicineUniversity of CologneInternational Genomics ConsortiumChildren's Hospital at WestmeadUniversity of VeronaPediatrics and GeneticsSeven Bridges Genomics (United States)University of PaduaCa' Foncello HospitalUniversity of LausanneThe Francis Crick InstituteGenome Institute of SingaporeInstitut Jules BordetPrincess Margaret Cancer CentreShadyside HospitalWellesley CollegeHefei University of TechnologyUniversity of AntwerpGZA Ziekenhuizen Campus Sint-AugustinusUniversity of PennsylvaniaCancer Research UK Cambridge CenterUniversity Hospital Southampton NHS Foundation TrustWellcome TrustProstate Cancer CanadaMedicon VillageIcelandic Cancer SocietyXijing HospitalAir Force Medical UniversityAustralian Institute of Tropical Health and MedicineJames Cook UniversityFondazione IRCCS Istituto Neurologico Carlo BestaBioplatforms AustraliaMRC Cancer UnitLondon CancerCancer Genomics CentrePrince Charles HospitalUniversity of FloridaBGI Group (China)Jackson LaboratoryThe Jackson Laboratory for Genomic MedicineCambridge University Hospitals NHS Foundation TrustUniversity of WürzburgUniversity of MiamiSylvester Comprehensive Cancer CenterSt Thomas' HospitalOsaka International Cancer InstituteWashington University in St. LouisAlvin J. Siteman Cancer CenterSkåne University HospitalNational Human Genome Research InstituteVictorian Comprehensive Cancer CentreLeibniz Institute of Virology (LIV)Government of IndiaDepartment of BiotechnologyMinistry of Science and TechnologyImperial College LondonGoethe University FrankfurtUC San Diego Health SystemMoores Cancer CenterWakayama Medical UniversityPeking UniversityChildren's Hospital of PhiladelphiaHallym UniversityInstitut de Biologia EvolutivaHokkaido UniversityTokyo National HospitalUniversity of Nebraska Medical CenterSyneos Health (South Korea)Amsterdam UMC Location University of AmsterdamHong Kong University of Science and TechnologyShenzhen Bioeasy Biotechnology (China)Charité - Universitätsmedizin BerlinBC Cancer AgencyEdinburgh Royal InfirmaryMax Delbrück CenterHanyang UniversityAsan Medical CenterChicago Department of Public HealthMcGill University and Génome Québec Innovation CentreCancer Research HorizonsInstitute of Genetics and CancerUniversity of EdinburghUniversity of ZagrebNational Cancer Centre JapanDmitry Rogachev National Research Center of Pediatric Hematology, Oncology and ImmunologyGeorge Washington UniversityMacquarie UniversityBarking, Havering And Redbridge University Hospitals NHS TrustEwha Womans UniversityDana-Farber Brigham Cancer CenterUniversity of GöttingenUniversity of Duisburg-EssenVan Andel InstituteRoyal Brisbane and Women's HospitalChildren's Medical Research InstituteInstitute of Biomedical Sciences, Academia SinicaMax Planck Institute for Molecular GeneticsBiobyte Solutions (Germany)Quantitative BioSciencesUniversity of OsloLeidos (United States)Leidos Biomedical Research Inc. (United States)Institute for Systems BiologyUniversidad de OviedoInstitut BergoniéOrthopädische PraxisDuke UniversityOxford Nanopore Technologies (United Kingdom)Mount Sinai HospitalLunenfeld-Tanenbaum Research InstituteHenry Ford HospitalKyushu UniversityHeidelberg Academy of Sciences and HumanitiesVector InstitutePenrose-St. Francis Health ServicesUniversity of BergenUniversity Hospital UlmGerman Cancer AidAddenbrooke's HospitalSt. Jude Children's Research HospitalCarleton CollegeKeio UniversitySage BionetworksRobert Bosch HospitalNottingham University Hospitals NHS TrustNYU Langone HealthCleveland ClinicMayo Clinic in FloridaChristiana Care Health SystemSRA International (United States)Guy's HospitalKing's College LondonKings Health PartnersInsermCentre Hospitalier Universitaire de BesançonInstitutul Clinic FundeniRoyal Surrey County HospitalNIHR Cambridge Biomedical Research CentreNinewells HospitalMedical College of WisconsinEmory UniversityVanderbilt UniversityThe Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research InstituteYokohama City UniversityUniversitätsklinikum Gießen und MarburgInstitut de Recherche en Cancérologie de MontpellierNorfolk and Norwich University HospitalAnalytical Biological Services (United States)Tata Memorial HospitalAdvanced Centre for Treatment, Research and Education in CancerUniversity of PittsburghEndeavor HealthJapan Agency for Medical Research and DevelopmentKorea UniversityWalter Reed National Military Medical CenterUniversity Hospitals Coventry and Warwickshire NHS TrustSankt-Antonius-Hospital EschweilerETH ZurichUniversity of IcelandChina National GeneBankSingapore General HospitalIstituto Tumori BariAgostino Gemelli University PolyclinicIstituti di Ricovero e Cura a Carattere ScientificoCommissariat à l'Énergie Atomique et aux Énergies AlternativesGenoscopeMaastricht UniversityUniversity Hospitals Birmingham NHS Foundation TrustQueen's University BelfastUniversity of SouthamptonWinship Cancer InstituteUniversity of LatviaInstitut CurieAugusta UniversityGeorgia Regents Medical CenterWythenshawe HospitalNationwide Children's HospitalInternational Institute for Molecular OncologyMRC University of Glasgow Centre for Virus ResearchHuazhong University of Science and TechnologyPeking University Cancer HospitalThe University of OsakaRuijin HospitalEastern HealthMonash UniversitySecond Military Medical UniversityUniversity of HoustonWestmead HospitalErasmus MC

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