DNA Methylation Profiles of Ovarian Epithelial Carcinoma Tumors and Cell Lines 英文参考文献.docVIP

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DNA Methylation Profiles of Ovarian Epithelial Carcinoma Tumors and Cell Lines 英文参考文献.doc

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DNA Methylation Profiles of Ovarian Epithelial Carcinoma Tumors and Cell Lines 英文参考文献

DNAMethylationProfilesofOvarianEpithelial CarcinomaTumorsandCellLines SaharHoushdaran1.,SarahHawley2.,ChanaPalmer2,MihaelaCampan1,3,MariN.Olsen4,AvivaP. Ventura5,BeatriceS.Knudsen5,CharlesW.Drescher5,NicoleD.Urban5,PatrickO.Brown4,PeterW. Laird1,3,6 * 1DepartmentofBiochemistryandMolecularBiology,UniversityofSouthernCalifornia,LosAngeles,California,UnitedStatesofAmerica,2CanaryFoundation,PaloAlto, California, United States of America, 3Department of Surgery, University of Southern California, Los Angeles, California, United States of America, 4Department of Biochemistry,StanfordUniversity,Stanford,California,UnitedStatesofAmerica,5FredHutchinsonCancerResearchCenter,Seattle,Washington,UnitedStatesofAmerica, 6UniversityofSouthernCaliforniaEpigenomeCenter,UniversityofSouthernCalifornia,LosAngeles,California,UnitedStatesofAmerica Abstract Background:EpithelialovariancarcinomaisasignificantcauseofcancermortalityinwomenworldwideandintheUnited States. Epithelial ovarian cancer comprises several histological subtypes, each with distinct clinical and molecular characteristics.Thenaturalhistoryofthisheterogeneousdisease,includingthecelltypesoforigin,ispoorlyunderstood. This study applied recently developed methods for high-throughput DNA methylation profiling to characterize ovarian cancercelllinesandtumors,includingrepresentativesofthreemajorhistologies. Methodology/Principal Findings: We obtained DNA methylation profiles of 1,505 CpG sites (808 genes) in 27 primary epithelialovariantumorsand15ovariancancercelllines.WefoundthattheDNAmethylationprofilesofovariancancercell linesweremarkedlydifferentfromthoseofprimaryovariantumors.AggregateDNAmethylationlevelsoftheassayedCpG sitestendedtobehigherinovariancancercelllinesrelativetoovariantumors.Withintheprimarytumors,thoseofthe samehistologicaltypeweremorealikeintheirmethylationprofilesthanthoseofdifferentsubtypes.Supervisedanalyses identified90CpGsites(68genes)thatexhibited‘subtype-specific’DNAmethylationpatterns(FDR,1%)amongth