表观遗传学在胃癌中的应用价值

:,,Emai:[e-mail]:,Emai:[e-mail];,Emai:[e-mail]李亚卓1,郭明洲2,赵坡1中国人民解放军总医院1.病理科;2.消化科,北京100853,DNARNA,DNA,;;DNA;;RNA:R735.2:A:1006-5709(2011)07-0589-05:2011-03-18ThevalueofepigeneticschangesinhumangastriccancerLIYazhuo1,GUOMingzhou2,ZHAOPo11.DepartmentofPathology;2.DepartmentofGastroenterology,PLAGeneralHospita,lBeijing100853,ChinaAbstractEpigeneticsisasubjectwhichfocusesongeneexpression,mainlyincludingDNAmethylation,histonemodificationsandnoncodingRNAs.Epigeneticsplaysanimportantroleingastriccancercarcinogenesis.Moreandmoreresearchersstarttofocusonepigeneticschangesingastriccancer.TheclinicalvalueofDNAmethylationchangeswasrecongizedwidely.Theepigenetictechniqueswillapplytoclinicfordiagnosis,prognosis,chemosensitivityandtreatmentofgastriccancer.Thisarticlemainlyfocusesondisscussionofthevalueofepigeneticschangesingastriccancer.KeywordsEpigenetics;Gastriccancer;DNAmethylation;Histonemodification;NoncodingRNA,,50%~75%,,5[15],DNARNA,,1(epigenetics),DNA,DNARNA(noncodingRNA)sumolation(smallubiquitinlikemodifier,SUMO)DNARNA2DNADNA[68],APCLKB1/STK11RASSF1ARB1P15INK4aP16INK4bp14ARFCHFRTHBS1DAPKcaspase8MGMTBRCA1hMLH1EcadherinVHLTIMP3RARB3DNA2.1CHFRDNA,(checkpoint)CHFR(checkpointwithFHAandringfinger),,CHFR,G2MCHFRG2M,,CHFRPlk1,Cdc25,,,CHFR,(Paclitaxel)(Nocodazole),;CHFR,58920117207ChinJGastroenterolHepato,lJul2011,Vol20,No7,;CHFR,,CHFR,,CHFR,[910]CHFR(52,5Aza2deoxycytidine,5AzaCdR),G2M[1114]Hu[6]70,MSP(methylationspecificpolymerasechainreaction)CHFR,CHFR,CHFRSatoh[15]CHFR39%,20%,DNA5aza2deoxycytidine(Docetaxel)PaclitaxelCHFR,DocetaxelPaclitaxel,,CHFR2.2RASSF1ARASSF1A3p21.3,LOHRASSF1A,RASSF1AcyclinDG1[1617];RASSF1AG2/M[18]Guo[19],RASSF1A58.7%,,,Kang[20]RASSF1A,EBRASSF1A66.7%,EB3.6%,EBRASSF1A,RASSF1A[21]Zhao[22]RASSF1A5(fluorouracil)(mitomycin)RASSF1A2.3MLH1(mismatchrepair,MMR),DNADNA[2324],DNADNAhMSH2hMLH12,[2526]MLH1,Plumb[27]MLH1,MLH1MLH1H.pylori,[28]2.4DNA,,,Correa[29],,,,,CDH1H.pylori[30]2.5DNA,DNA,Sugita[31],80,BNIPDAPK,Park[32]Du[33],RECK,Sakakuar[34]RTQMSPRUNX3,RUNX33,N,/[35](histoneacetyltransferase,HAT);(histonedeacetylase,HDAC)HATHDAC,,[3637],,H3H4Chen[38],59020117207ChinJGastroenterolHepato,lJul2011,Vol20,No7RhoE,DNA,RhoEMitani[39],p21WAF1/CIP1H3,p21WAF1/CIP1Hamai[40],HLTF5CpGHLTFMeng[41]H3K9SGC7901MGC803p16MLH1DNA,H3K94,,,5azacytidine(5AzaCR)5AzaCdR,azacitadine(Vidaza)decitabine(Dacogen)FDA(MDS)[42],5,DNA,DNMTs[4344]60%MDSazacitadine,MDS,decitabine70%[4546][47],HDAC,,[48]HDAC4:(hydroxamicacids)(cyclicpeptides)(shortchainfattyacids)(benzamides)HDAC18,4,,HDACHDACs[4950]HDAC,[51]HDACTSASAHAMS275CI994HDAC,DNMTHDAC,;TSA5AzadC5AzadC,[52]5AzadCTSA,HDAC,Yoon[53],HDAC(SAHAPXD101CG2)(),,PXD101,5NoncodingRNA2%RNA,98%RNARNARNA,RNA,,MicroRNA5.1MicroRNANoncodingRNA,MicroRNAMicroRNA(miRNA)RNA,NoncodingRNAmiRNARNA1RNA,dsRNADorsha70ntpremiRNA;premiRNA,dsRNAdicer19~26ntRNA,RNAmRNA3UTR[54]miRNAMicroRNA,miRNAZhang[55]miR21,miR21H.pylori;AGS,miR21,miR21;RECKmiR21,RECKPetrocca[56]miR106b25TGFOtsubo[57]miR126,SOX2,5.2miRNAmiRNA,,,,miRNAXia[58](MDR)SGC7901/VCRmiR15bmiR16BCL259120117207ChinJGastroenterolHepato,lJul2011,Vol20,No7Liu[59]miR1miR20amiR27amiR34miR4235p,6,,,RNA,RNA[1]RoderDM.Theepidemiologyofgastriccancer[J].GastricCancer,2002,5(Suppl1):511.[2]JemalA,SiegelR,XuJ,eta.lCancerstatistics[J].CACancerJClin,2010,6(5):277300.[3]WongBC,ChingCK,LamSK,eta.lDifferentialnorthtosouthgastriccancerduodenalulcergradientinChina[J].JGastroenterolHepato,l1998,13(10):10501057.[4]KelleyJR,DugganJM.Gastriccancerepidemiologyandriskfactors[J].JClinEpidemio,l2003,56(1):19.[5]StewartBW,KleihuesP.Globalincidenceofstomachcancerinmen;thehighestratesoccurinEasternAsia,SouthAmericaandEasternEurope[M].Lyon:InternationalAgencyforResearchonCancerPress,2003:194.[6]HuSL,KongXY,ChengZD,eta.lPromotermethylationofp16,Runx3,DAPKandCHFRgenesisfrequentingastriccarcinoma[J].Tumor,i2010,96(5):726733.[7]HirakiM,KitajimarY,SatoS,eta.lAberrantgenemethylationintheperitonealfluidisariskfactorpredictingperitonealrecurrenceingastriccancer[J].WorldJGastroentero,l2010,16(3):330338.[8]TamuraG.Alterationsoftumorsuppressorandtumorrelatedgenesinthedevelopmentandprogressionofgastriccancer[J].WorldJGastroentero,l2006,12(2):192198.[9]KangHC,KmiIJ,ParkJH,eta.lPromoterhypermethylationandsilencingofCHFRmitoticstresschechpointgeneinhumangastriccancer[J].OncelRep,2004,12(1):129133.[10]MoriokaY,HibiK,SakaiM,eta.lAberrantmethylationoftheCHFRgeneindigestivetractcancer[J].AnticancerRes,2006,26(3A):17911795.[11]CornPG,HeathEI,HeitmillerR,eta.lFrequenthypermethylationofthe5CpGislandofEcadherininesophagealadenocarcinoma[J].ClinCancerRes,2001,7(9):27652769.[12]ToyotaM,SasakiY,SatohA,eaa.lEpigneticinactivationofCHFRinhumantumors[J].ProcNatlAcadSciUSA,2003,100(13):78187823.[13]SouttoM,PengD,RazviM,eta.lEpigeneticandgeneticsilencingofCHFRinesophagealadenocarcinomas[J].Cancer,2010,116(17):40334042.[14]HondaT,TamuraG,WakiT,eta.lPromoterhypermethylationoftheCHFRgeneinneplasticandnonneoplasticgastricepithelia[J].BrJCancer,2004,90(10):20132016.[15]SatohA,ToyotaM,ItohF,e