MicroRNA Profiling of BRCA12 Mutation-Carrying and Non-Mutation-Carrying High-Grade Serous Carcinomas of Ovary 英文参考文献.docVIP

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MicroRNA Profiling of BRCA12 Mutation-Carrying and Non-Mutation-Carrying High-Grade Serous Carcinomas of Ovary 英文参考文献.doc

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MicroRNA Profiling of BRCA12 Mutation-Carrying and Non-Mutation-Carrying High-Grade Serous Carcinomas of Ovary 英文参考文献

MicroRNAProfilingofBRCA1/2Mutation-Carryingand Non-Mutation-CarryingHigh-GradeSerousCarcinomas ofOvary Cheng-HanLee1*,SubbayaSubramanian2,AndrewH.Beck3,InigoEspinosa3,JanineSenz4,ShirleyX. Zhu3,DavidHuntsman4,MattvandeRijn3,C.BlakeGilks1 1DepartmentofPathologyLaboratoryMedicine,UniversityofBritishColumbia,VancouverGeneralHospital,Vancouver,BritishColumbia,Canada,2Departmentof LaboratoryMedicineandPathology,UniversityofMinnesota,Minneapolis,Minnesota,UnitedStatesofAmerica,3DepartmentofPathology,StanfordUniversityMedical Center,Stanford,California,UnitedStatesofAmerica,4DepartmentofPathologyLaboratoryMedicine,BritishColumbiaCancerAgency,Vancouver,BritishColumbia, Canada Abstract Background: MicroRNAs (miRNA) are 20,25 nucleotidenon-coding RNAs that inhibit thetranslation of targeted mRNA, and they have been implicated in the development of human malignancies. High grade serous ovarian carcinomas, the mostcommonandlethalsubtypeofovariancancer,canoccursporadicallyorinthesettingofBRCA1/2syndromes.Littleis known regarding the miRNA expression profiles of high grade serous carcinoma in relation to BRCA1/2 status, and comparedtonormaltubalepithelium,theputativetissueoforiginforhighgradeserouscarcinomas. Methodology/Principal Findings:GlobalmiRNAexpressionprofilingwasperformedonaseriesof33highgradeserous carcinomas,characterizedwithrespecttoBRCA1/2status(mutation,epigeneticsilencingwithlossofexpressionornormal), andwithclinicalfollow-up,togetherwith2lowgradeserouscarcinomas,2serousborderlinetumors,and3normalfallopian tube samples, using miRNA microarrays (328 human miRNA). Unsupervised hierarchical clustering based on miRNA expression profiles showed no clear separation between the groups of carcinomas with different BRCA1/2 status. There wererelativelyfewmiRNAsthatweredifferentiallyexpressedbetweenthegenotypicsubgroups.Comparisonof33high gradeserouscarcinomasto3normalfallopiantubesamplesidentifiedseveraldysregulatedmiRNAs(falsediscoveryrate ,5%),includingmiR-422bandmiR-34