Mutational Profiling of Kinases in Human Tumours of Pancreatic Origin Identifies Candidate Cancer Genes in Ductal and Ampulla of Vater Carcinomas 英文参考文献.docVIP

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Mutational Profiling of Kinases in Human Tumours of Pancreatic Origin Identifies Candidate Cancer Genes in Ductal and Ampulla of Vater Carcinomas 英文参考文献.doc

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Mutational Profiling of Kinases in Human Tumours of Pancreatic Origin Identifies Candidate Cancer Genes in Ductal and Ampulla of Vater Carcinomas 英文参考文献

MutationalProfilingofKinasesinHumanTumoursof PancreaticOriginIdentifiesCandidateCancerGenesin DuctalandAmpullaofVaterCarcinomas VincenzoCorbo1,RossanaRitelli1,StefanoBarbi2,NiccolaFunel3,DanielaCampani3,AlbertoBardelli4, AldoScarpa1,2 * 1ARC-NETResearchCenter,UniversityofVerona,PoliclinicoG.B.Rossi,Verona,Italy,2DepartmentofPathology,UniversityofVerona,PoliclinicoG.B.Rossi,Verona,Italy, 3DepartmentofPathology,UniversityofPisa,Pisa,Italy,4LaboratoryofMolecularGenetics,InstituteforCancerResearchandTreatment,UniversityofTorinoMedical School,Candiolo,Italy Abstract Background:Proteinkinasesarekeyregulatorsofcellularprocesses(suchasproliferation,apoptosisandinvasion)thatare oftenderegulatedinhumancancers.Accordingly,kinasegeneshavebeenthefirsttobesystematicallyanalyzedinhuman tumorsleadingtothediscoverythatmanyoncogenescorrespondtomutatedkinases.Inmostcasesthegeneticalterations translateinconstitutivelyactivekinaseproteins,whichareamenableoftherapeutictargeting.Tumoursofthepancreasare aggressiveneoplasmsforwhichnoeffectivetherapeuticstrategyiscurrentlyavailable. Methodology/PrincipalFindings:WeconductedaDNA-sequenceanalysisofaselectedsetof35kinasegenesinapanelof 52pancreaticexocrineneoplasms,including36pancreaticductaladenocarcinoma,and16ampullaofVatercancer.Among otherchangeswefoundsomaticmutationsinATM,EGFR,EPHA3,EPHB2,andKIT,noneofwhichwaspreviouslydescribedin cancers. Conclusions/Significance: Although the alterations identified require further experimental evaluation, the localization withindefinedproteindomainsindicatesfunctionalrelevanceformostofthem.Someofthemutatedgenes,includingthe tyrosine kinases EPHA3 and EPHB2, are clearly amenable to pharmacological intervention and could represent novel therapeutictargetsfortheseincurablecancers. Citation:CorboV,RitelliR,BarbiS,FunelN,CampaniD,etal.(2010)MutationalProfilingofKinasesinHumanTumoursofPancreaticOriginIdentifiesCandidate CancerGenesinDuctalandAmpullaofVaterCarcinomas.PLoSONE5(9):e12653.doi:10.1371/journal.po