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1、ARTICLEdoi:10.1038/nature11404ComprehensivegenomiccharacterizationofsquamouscelllungcancersTheCancerGenomeAtlasResearchNetwork*Lungsquamouscellcarcinomaisacommontypeoflungcancer,causingapproximately400,000deathsperyearworldwide.Genomicalterationsinsquamouscelllungcancershavenotbeencompr
2、ehensivelycharacterized,andnomolecularlytargetedagentshavebeenspecificallydevelopedforitstreatment.AspartofTheCancerGenomeAtlas,hereweprofile178lungsquamouscellcarcinomastoprovideacomprehensivelandscapeofgenomicandepigenomicalterations.Weshowthatthetumourtypeischaracterizedbycomplexgeno
3、micalterations,withameanof360exonicmutations,165genomicrearrangements,and323segmentsofcopynumberalterationpertumour.Wefindstatisticallyrecurrentmutationsin11genes,includingmutationofTP53innearlyallspecimens.Previouslyunreportedloss-of-functionmutationsareseenintheHLA-AclassImajorhistoco
4、mpatibilitygene.SignificantlyalteredpathwaysincludedNFE2L2andKEAP1in34%,squamousdifferentiationgenesin44%,phosphatidylinositol-3-OHkinasepathwaygenesin47%,andCDKN2AandRB1in72%oftumours.Weidentifiedapotentialtherapeutictargetinmosttumours,offeringnewavenuesofinvestigationforthetreatmento
5、fsquamouscelllungcancers.Lungcanceristheleadingcauseofcancer-relatedmortalityworldwide,adjacent,histologicallynormaltissuesresectedatthetimeofsurgeryleadingtoanestimated1.4milliondeathsin2010(ref.1).Thediscovery(n5137)orfromperipheralblood(n541).Allpatientsprovidedofrecurrentmutationsin
6、theepidermalgrowthfactorreceptor(EGFR)writteninformedconsenttoconductgenomicstudiesinaccordancekinase,aswellasfusionsinvolvinganaplasticlymphomakinase(ALK),withlocalInstitutionalReviewBoards.Thedemographiccharacteris-hasledtoamarkedchangeinthetreatmentofpatientswithlungticsaredescribedi
7、nSupplementaryTable1.2.Themedianfollow-up2–5adenocarcinoma,themostcommontypeoflungcancer.Morerecentforthecohortwas15.8months,and60%ofpatientswerealiveatthedatahavesuggestedthattargetingmutationsinBRAF,AKT1,ERBB2timeofthelastfollow-up(dataupdatedinNovember2011).Ninety-sixandPIK3
