Quantitative Methylation Profiles for Multiple Tumor Suppressor Gene Promoters in Salivary Gland Tumors 英文参考文献.docVIP

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Quantitative Methylation Profiles for Multiple Tumor Suppressor Gene Promoters in Salivary Gland Tumors 英文参考文献.doc

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Quantitative Methylation Profiles for Multiple Tumor Suppressor Gene Promoters in Salivary Gland Tumors 英文参考文献

QuantitativeMethylationProfilesforMultipleTumor SuppressorGenePromotersinSalivaryGlandTumors MeganL.Durr1,WojciechK.Mydlarz1,ChunboShao1,MariannaL.Zahurak2,AliceY.Chuang1, MohammadO.Hoque1,WilliamH.Westra3,NanetteJ.Liegeois4,JosephA.Califano1,5 ,David Sidransky1,PatrickK.Ha1,5* 1Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institution, Baltimore, Maryland, United States of America, 2Division of Oncology Biostatistics, Department of Oncology, Johns Hopkins Medical Institution, Baltimore, Maryland, United States of America, 3Department of Pathology, Johns Hopkins MedicalInstitution,Baltimore,Maryland,UnitedStatesofAmerica,4DepartmentofOncology,JohnsHopkinsMedicalInstitution,Baltimore,Maryland,UnitedStatesof America,5MiltonJ.Dance,Jr.HeadandNeckCenter,GreaterBaltimoreMedicalCenter,Baltimore,Maryland,UnitedStatesofAmerica Abstract Background:Methylationprofilingoftumorsuppressorgene(TSGs)promotersisquicklybecomingapowerfuldiagnostic toolfortheearlydetection,prognosis,andevenpredictionofclinicalresponsetotreatment.Fewstudiesaddressthisin salivaryglandtumors(SGTs);hencethepromotermethylationprofileofvariousTSGswasquantitativelyassessedinprimary SGTtissuetodetermineiftumor-specificalterationscouldbedetected. Methodology:DNAisolatedfrom78tumorand17normalparotidglandspecimenswasassayedforpromotermethylation statusof19TSGsbyfluorescence-based,quantitativemethylation-specificPCR(qMSP).Thedatawereutilizedinabinary fashionaswellasquantitatively(usingamethylationquotient)allowingforbetterprofilingandinterpretationofresults. Principal Findings: The average number of methylation events across the studied genes was highest in salivary duct carcinoma(SDC),withamethylationvalueof9.6,comparedtothenormal4.5(p,0.0003).Therewasavariablefrequencyand individualmethylationquotientdetected,dependingontheTSGandthetumortype.Whencomparingnormal,benign,and malignantSGTs,therewasastatisticallysignificanttrendforincreasingmethylationinAPC,Mint1,PGP9.5,RAR-b,andTimp3.