Correlation between promoter methylation of p14ARF, TMS1ASC, and DAPK, and p53 mutation with prognosis in cholangiocarcinoma.docVIP

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Correlation between promoter methylation of p14ARF, TMS1ASC, and DAPK, and p53 mutation with prognosis in cholangiocarcinoma.doc

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Correlation between promoter methylation of p14ARF, TMS1ASC, and DAPK, and p53 mutation with prognosis in cholangiocarcinoma

Xiaofangetal.WorldJournalofSurgicalOncology2012,10:5 /content/10/1/5 WORLD JOURNAL OF SURGICAL ONCOLOGY RESEARCH OpenAccess Correlationbetweenpromotermethylationof ARF p14 ,TMS1/ASC,andDAPK,andp53mutation withprognosisincholangiocarcinoma * LiuXiaofang,TangKun,YuShaoping,WangZaiqiuandSuHailong Abstract Background:Tostudythemethylationstatusofgenesthatplayaroleinthep53-Baxmitochondrialapoptosis pathwayanditsclinicalsignificanceincholangiocarcinoma. PatientsandMethods:Outof36casescholangiocarcinomapatientsfromApril2000toMay2005werecollected. PromoterhypermethylationofDAPK,p14ARF,andASCweredetectedbymethylation-specificPCRon cholangiocarcinomaandnormaladjacenttissuessamples.Mutationofthep53genewasexaminedbyautomated sequencing.Correlationbetweenmethylationofthesegenesand/orp53mutationstatuswithclinical characteristicsofpatientswasinvestigatedbystatisticalanalysis. Results:Wefound66.7%of36cholangiocarcinomapatientshadmethylationofatleastoneofthetumorsuppressor genesanalyzed.p53genemutationwasfoundin22of36patients(61.1%).Combinedp53mutationandDAPK,p14ARF , and/orASCmethylationwasdetectedin14cases(38.9%).Therewerestatisticallysignificantdifferencesintheextentof pathologicbiology,differentiation,andinvasionbetweenpatientswithcombinedp53mutationandDAPK,p14ARF ,and/ orASCmethylationcomparedtothosewithout(P0.05).ThesurvivalrateofpatientswithcombinedDAPK,p14ARF , andASCmethylationandp53mutationwaspoorerthanotherpatients(P0.05). Conclusion:OurstudyindicatesthatmethylationofDAPK,p14ARF,andASCincholangiocarcinomaisacommon event.Furthermore,p53mutationcombinedwithDAPK,p14ARF,and/orASCmethylationcorrelateswithmalignancy andpoorprognosis. Keywords:cholangiocarcinoma,methylation-specificPCR,p53-Baxmitochondrialapoptosispathway Background wellstudiedincholangiocarcinomatodate.Thus,investi- Apoptosisorprogrammedcelldeathisanormalphysiolo- gationofthemethylationstatusofthegenesinthispath- gical control mechanism that iscritical inmaintaining way may give insight into the me