CBL Is Frequently Altered in Lung Cancers Its Relationship to Mutations in MET and EGFR Tyrosine Kinases 英文参考文献.docVIP

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CBL Is Frequently Altered in Lung Cancers Its Relationship to Mutations in MET and EGFR Tyrosine Kinases 英文参考文献.doc

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CBL Is Frequently Altered in Lung Cancers Its Relationship to Mutations in MET and EGFR Tyrosine Kinases 英文参考文献

CBLIsFrequentlyAlteredinLungCancers:Its RelationshiptoMutationsinMETandEGFRTyrosine Kinases Yi-HungCarolTan1,SoundararajanKrishnaswamy2,SuvobrotoNandi2,RajaniKanteti2,SapanaVora3, KenanOnel3,RifatHasina2,Fang-YiLo1,EssamEl-Hashani2,GustavoCervantes2,MatthewRobinson2, StephenC.Kales4,StanleyLipkowitz4,TheodoreKarrison5,MartinSattler6,EverettE.Vokes2 ,Yi-Ching Wang7,RaviSalgia2* 1Department of Life Science, National Taiwan Normal University, Taipei, Taiwan, 2Department of Medicine, The University of Chicago Cancer Research Center, The UniversityofChicagoMedicalCenter,PritzkerSchoolofMedicine,Chicago,Illinois,UnitedStatesofAmerica,3DepartmentofPediatrics,TheUniversityofChicagoCancer ResearchCenter,TheUniversityofChicagoMedicalCenter,PritzkerSchoolofMedicine,Chicago,Illinois,UnitedStatesofAmerica,4LaboratoryofCellularandMolecular Biology,CenterforCancerResearch,NationalCancerInstitute,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica,5DepartmentofStatistics,The UniversityofChicago,Chicago,Illinois,UnitedStatesofAmerica,6DepartmentofMedicalOncology,Dana-FarberCancerInstituteandHarvardMedicalSchool,Boston, Massachusetts,UnitedStatesofAmerica,7DepartmentofPharmacology,CollegeofMedicine,NationalChengKungUniversity,Tainan,Taiwan Abstract Background: Non-small cell lung cancer (NSCLC) is a heterogeneous group of disorders with a number of genetic and proteomicalterations.c-CBLisanE3ubiquitinligaseandadaptormoleculeimportantinnormalhomeostasisandcancer.We determinedthegeneticvariationsofc-CBL,relationshiptoreceptortyrosinekinases(EGFRandMET),andfunctionalityinNSCLC. Methods and Findings: Using archival formalin-fixed paraffin embedded (FFPE) extracted genomic DNA, we show that c-CBLmutationsoccurinsomaticfashionforlungcancers.c-CBLmutationswerenotmutuallyexclusiveofMETorEGFR mutations; however they were independent of p53 and KRAS mutations. In normal/tumor pairwise analysis, there was significantlossofheterozygosity(LOH)forthec-CBLlocus(22%,n=8/37)andnoneof