Promoter DNA Methylation of Oncostatin M receptor-β as a Novel Diagnostic and Therapeutic Marker in Colon Cancer 英文参考文献.docVIP

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Promoter DNA Methylation of Oncostatin M receptor-β as a Novel Diagnostic and Therapeutic Marker in Colon Cancer 英文参考文献.doc

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Promoter DNA Methylation of Oncostatin M receptor-β as a Novel Diagnostic and Therapeutic Marker in Colon Cancer 英文参考文献

PromoterDNAMethylationofOncostatinMreceptor-b asaNovelDiagnosticandTherapeuticMarkerinColon Cancer MyoungSookKim1,JoostLouwagie2,BeatrizCarvalho3,JochimS.TerhaarsiveDroste4,HannahLui Park1,YoungKwangChae5,KeishiYamashita1,JunweiLiu1,KimberlyLaskieOstrow1,ShizhangLing6, RafaelGuerrero-Preston1,SemraDemokan1,ZubeydeYalniz7,NejatDalay7,GerritAMeijer3,WimVan Criekinge2,DavidSidransky1* 1Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America, 2OncoMethylome SciencesS.A,CHUNiveau+4Tour4dePharmacie(ba?timent36),Liege,Belgium,3DepartmentofPathology,FreeUniversityofAmsterdam,Amsterdam,TheNetherlands, 4DepartmentofGastroenterology,FreeUniversityofAmsterdam,Amsterdam,TheNetherlands,5DepartmentofMedicine,AlbertEinsteinMedicalCenter,Philadelphia, Pennsylvania,UnitedStatesofAmerica,6DepartmentofPathology,TheJohnsHopkinsSchoolofMedicine,Baltimore,Maryland,UnitedStatesofAmerica,7Oncology institute,IstanbulUniversity,Istanbul,Turkey Abstract Inadditiontogeneticchanges,theoccurrenceofepigeneticalterationsisassociatedwithaccumulationofbothgeneticand epigenetic events that promote the development and progression of human cancer. Previously, we reported a set of candidategenesthatcomprisepartoftheemerging‘‘cancermethylome’’.Inthepresentstudy,wefirsttested23candidate genesforpromotermethylationinasmallnumberofprimarycolontumortissuesandcontrols.Basedontheseresults,we thenexaminedthemethylationfrequencyofOncostatinMreceptor-b(OSMR)inalargernumberoftissueandstoolDNA samples collected from colon cancer patients and controls. We found that OSMR was frequently methylated in primary coloncancertissues(80%,80/100),butnotinnormaltissues(4%,4/100).MethylationofOSMRwasalsodetectedinstool DNAfromcolorectalcancerpatients(38%,26/69)(cut-offinTaqMan-MSP,4).Detectionofothermethylatedmarkersinstool DNAimprovedsensitivitywithlittleeffectonspecificity.PromotermethylationmediatedsilencingofOSMRincelllines,and CRC cells with