Genomic Profiling Identifies GATA6 as a Candidate Oncogene Amplified in Pancreatobiliary Cancer 英文参考文献.docVIP

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Genomic Profiling Identifies GATA6 as a Candidate Oncogene Amplified in Pancreatobiliary Cancer 英文参考文献.doc

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Genomic Profiling Identifies GATA6 as a Candidate Oncogene Amplified in Pancreatobiliary Cancer 英文参考文献

GenomicProfilingIdentifiesGATA6asaCandidate OncogeneAmplifiedinPancreatobiliaryCancer KevinA.Kwei1.,MuraliD.Bashyam1,2,3.,JessicaKao1,RamanRatheesh2,EdumakantiC.Reddy3, YoungH.Kim1,KelliMontgomery1,CraigP.Giacomini1,Yoon-LaChoi1,4,SreejataChatterjee2,CollinsA. Karikari5,KeyanSalari1,6,PeiWang7,TinaHernandez-Boussard6,GowrishankarSwarnalata8,Mattvan deRijn1,AnirbanMaitra5,JonathanR.Pollack1* 1DepartmentofPathology,StanfordUniversity,Stanford,California,UnitedStatesofAmerica,2LaboratoryofMolecularOncology,CentreforDNAFingerprintingand Diagnostics,Nacharam,Hyderabad,India,3NationalGenomicsandTranscriptomicsFacility,CentreforDNAFingerprintingandDiagnostics,Nacharam,Hyderabad,India, 4DepartmentofPathology,SamsungMedicalCenter,SungkyunkwanUniversitySchoolofMedicine,Seoul,SouthKorea,5DepartmentofPathology,TheJohnsHopkins University,Baltimore,Maryland,UnitedStatesofAmerica,6DepartmentofGenetics,StanfordUniversity,Stanford,California,UnitedStatesofAmerica,7DivisionofPublic HealthSciences,FredHutchinsonCancerResearchCenter,Seattle,Washington,UnitedStatesofAmerica,8DepartmentofPathology,ApolloHospitals,Hyderabad,India Abstract Pancreatobiliary cancers have among the highest mortality rates of any cancer type. Discovering the full spectrum of moleculargeneticalterationsmaysuggestnewavenuesfortherapy.Tocataloguegenomicalterations,wecarriedoutarray- basedgenomicprofilingof31exocrinepancreaticcancersand6distalbileductcancers,expandedasxenograftstoenrich thetumorcellfraction.WeidentifiednumerousfocalDNAamplificationsanddeletions,includingin19%ofpancreatobiliary casesgainatcytoband18q11.2,alocusuncommonlyamplifiedinothertumortypes.Thesmallestsharedamplificationat 18q11.2 included GATA6,atranscriptional regulator previouslylinked tonormalpancreas development. Whenamplified, GATA6wasoverexpressedatboththemRNAandproteinlevels,andstrongimmunostainingwasobservedin25of54(46%) primarypancreaticcancerscomparedto0of33normalpancreasspecimenssurveyed.GATA6expressioninxenograftswas associate