Recurrent Genomic Gains in Preinvasive Lesions as a Biomarker of Risk for Lung Cancer 英文参考文献.docVIP

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Recurrent Genomic Gains in Preinvasive Lesions as a Biomarker of Risk for Lung Cancer 英文参考文献.doc

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Recurrent Genomic Gains in Preinvasive Lesions as a Biomarker of Risk for Lung Cancer 英文参考文献

RecurrentGenomicGainsinPreinvasiveLesionsasa BiomarkerofRiskforLungCancer PierreP.Massion1*,YongZou1,HasmetUner3,PorntipKiatsimkul2,HollyJ.Wolf3,AnnaE.Baron3, TimByers3,SteinnJonsson6,StephenLam7,FredR.Hirsch2,4,YorkE.Miller5,WilburA.Franklin4, MarileilaVarella-Garcia2 1DivisionofAllergy,PulmonaryandCriticalCareMedicine,VanderbiltIngramCancerCenter,VeteransAdministrationMedicalCenter,Nashville,Tennessee,UnitedStates ofAmerica,2DepartmentofMedicine,UniversityofColoradoDenver,Denver,Colorado,UnitedStatesofAmerica,3DepartmentofPreventiveMedicineandBiostatistics, UniversityofColoradoDenver,Denver,Colorado,UnitedStatesofAmerica,4DepartmentofPathology,UniversityofColoradoDenver,Denver,Colorado,UnitedStatesof America,5PulmonaryDivision,DepartmentofMedicine,DenverVeteransAffairsMedicalCenterDenver,Denver,Colorado,UnitedStatesofAmerica,6Departmentof MedicineUniversityofIcelandHospitals,Reykjavik,Iceland,7DepartmentofRespiratoryMedicine,UniversityofBritishColumbia,Vancouver,Canada Abstract Lungcarcinomadevelopmentisaccompaniedbyfieldchangesthatmayhavediagnosticsignificance.Wehavepreviously showntheimportanceofchromosomalaneusomyinlungcancerprogression.Here,wetestedwhethergenomicgainsinsix specificloci,TP63on3q28,EGFRon7p12,MYCon8q24,5p15.2,andcentromericregionsforchromosomes3(CEP3)and6 (CEP6), may provide further value in the prediction of lung cancer. Bronchial biopsy specimens were obtained by LIFE bronchoscopyfrom70subjects(27withprevalentlungcancersand43individualswithoutlungcancer).Twentysixbiopsies werereadasmoderatedysplasia,21asseveredysplasiaand23ascarcinomainsitu(CIS).Four-micronparaffinsectionswere submittedtoa4-targetFISHassay(LAVysion,AbbottMolecular)andreprobedforTP63andCEP3sequences.Spotcounts were obtained in 30–50 nuclei per specimen for each probe. Increased gene copy number in 4 of the 6 probes was associatedwithincreasedriskofbeingdiagnosedwithlungcancerbothinunadjustedanalyses(oddsratio=11,p,0.05) andadjustedforhistologygrade(oddsratio=17,p,0.05).Themos