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ID:40384545
大小:1.82 MB
页数:9页
时间:2019-08-01
《Nature_Recurrent somatic mutations in regulatory regions of human》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、analysisRecurrentsomaticmutationsinregulatoryregionsofhumancancergenomesCollinMelton1,2,JasonAReuter1,DamekVSpacek1&MichaelSnyder1AberrantregulationofgeneexpressionincancercanpromoteAlthoughthemajorityofsequencingstudiesincancerhavefocusedsurvivalandproliferat
2、ionofcancercells.Hereweintegrateonprotein-codingsequences,onlyasmallfractionofthegenomewhole-genomesequencingdatafromTheCancerGenomeAtlasencodesprotein.Oftheremaininggenomicsequence,alargeportion(TCGA)for436patientsfrom8cancersubtypeswithENCODEcontainsregulato
3、ryelements4.Itispossiblethatdrivermutationsandotherregulatoryannotationstoidentifypointmutationsinregulatoryelementsexistthatdysregulateoncogenesandtumorinregulatoryregions.Wefindevidenceforpositiveselectionsuppressors.Recently,anexampleofaregulatorymutationin
4、ofmutationsintranscriptionfactorbindingsites,consistentcancerwasidentifiedintheregulatoryregionupstreamoftheTERTwiththesesitesregulatingimportantcancercellfunctions.gene(encodingtelomerasereversetranscriptase)5,6.Furthermore,Usinganewmethodthatadjustsforsample
5、-andgenomicWeinholdetal.7identifiedrecurrentregulatorymutationsmodulat-locus–specificmutationrates,weidentifyrecurrentlymutatedingtheexpressionofPLEKHS1,WDR74andSDHDinananalysisofsitesacrossindividualswithcancer.Mutatedregulatorysitesmutationsinpromotersandenh
6、ancers.Fredrikssonetal.8identifiedincludeknownsitesintheTERTpromoterandmanynewrecurrentmutationsinproximitytogenetranscriptionalstartsitessites,includingasubsetinproximitytocancer-relatedgenes.(TSSs),althoughonlyTERTmutationsweresignificantlyassociatedInreport
7、erassays,twonewsitesdisplaydecreasedenhancerwithalteredmRNAtranscriptlevels.Thusfar,agenome-wideanalysisactivityuponmutation.Thesedatademonstratethatmanyofpotentialrecurrentmutationsinallannotatedregulatoryregionsregulatoryregionscontainmutationsunderselective
8、pressurehasyettobeperformed.andsuggestagreaterroleforregulatorymutationsincancerTheEncyclopediaofDNAElements(ENCODE)Projectisathanpreviouslyappreciated.NationalHumanGenomeResearchI
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