Integrated analyses of DNA methylation and hydroxymethylation reveal tumor suppressive roles of ECM1

Integrated analyses of DNA methylation and hydroxymethylation reveal tumor suppressive roles of ECM1, ATF5, and EOMES in human hepatocellular carcinoma

Gaoetal.GenomeBiology2014,15:533doc.xuehai.net

IntegratedanalysesofDNAmethylationandhydroxymethylationrevealtumorsuppressiverolesofECM1,ATF5,andEOMESinhumanhepatocellularcarcinoma

FeiGao1* ,YudongXia1 ,JunwenWang1,ZhilongLin1,YingOu2,3,XingLiu2,3,WeilongLiu4,5,BopingZhou4,5,HuijuanLuo1,BaojinZhou1,BoWen1,XiuqingZhang1andJianHuang2,3,5*

Background

Hepatocellularcarcinoma(HCC),whichisfrequentlycausedbyhepatitisvirus(BandC)infectionandalcoholabuse,isthemostcommontypeofprimarylivercancerandthirdleadingcauseofcancerdeathworldwide[1,2].AlthoughsurgicalandchemotherapeutictreatmentofHCCisevolving,surgicalresectionremainsthetreatmentofchoiceformanypatients.SurgicalresectionforHCCpatientsisassociatedwitha5-yearsurvivalrateof50%;however,thereisa70%recurrencerate[3].

*Correspondence:flys828@gmail.com;huangjchgc@hotmail.com

Equalcontributors1

BGI-Shenzhen,Shenzhen518083,China2

NationalEngineeringCenterforBiochipatShanghai,Shanghai201203,China

Fulllistofauthorinformationisavailableattheendofthe

article

ThemechanismunderlyingHCCdevelopmentremainspoorlyunderstood.Itiswidelyacceptedthataccumulatinggeneticalterationssuchaschromosomalalterations,geneamplifications,andmutationsareassociatedwithHCC[4,5].Furthermore,epigeneticalterations,particularlyab-normalDNAmethylationatthe5positionofcytosine(5mC),havebeenextensivelystudied[6].DNAhypome-thylationincancercellsisthoughttoleadtochromo-somalinstabilityandoncogeneactivation[7]andhasgenerallybeenregardedasahighlystableclinicalmarkerforcancer[8].Moreimportantly,anumberofstudieshavereportedthatthehypermethylationoftumorsuppressorgenes(TSGs)contributestoHCCpathogenesis[9-11].Thus,theaccuratedetectionofDNAmethylationmayprovidepowerfulmechanisticinsightintohepatocarcino-genesisandmayhaveapotentialapplicationfortheclin-icaldiagnosisofHCC.

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