Nucleosomes Correlate with In Vivo Progression Pattern of De Novo Methylation of p16 CpG Islands in Human Gastric Carcinogenesis 英文参考文献.docVIP
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Nucleosomes Correlate with In Vivo Progression Pattern of De Novo Methylation of p16 CpG Islands in Human Gastric Carcinogenesis 英文参考文献
NucleosomesCorrelatewithInVivoProgressionPattern
ofDeNovoMethylationofp16CpGIslandsinHuman
GastricCarcinogenesis
Zhe-MingLu1*,JingZhou1,XiuhongWang1,ZhenpoGuan1,HuaBai1,Zhao-JunLiu1,NaSu1,
KaifengPan2,JiafuJi3,DajunDeng1*
1KeyLaboratoryofCarcinogenesisandTranslationalResearch,MinistryofEducation,DivisionofCancerEtiology,PekingUniversityCancerHospitalandInstitute,Beijing,
China,2DepartmentofEpidemiology,PekingUniversityCancerHospitalandInstitute,Beijing,China,3DepartmentofSurgery,PekingUniversityCancerHospitaland
Institute,Beijing,China
Abstract
Background: The exact relationship between nucleosome positioning and methylation of CpG islands in human
pathogenesisisunknown.
Methodology/Principal Findings: In the present study, we characterized the nucleosome position within the p16 CpG
islandandestablishedaseedingmethylation-specificPCR(sMSP)assaybasedonbisulfitemodificationtoenrichthep16
allelescontainingmethylated-CpGatthemethylation‘‘seeding’’siteswithinitsintron-1ingastriccarcinogenesis.ThesMSP-
positiverateinprimarygastriccarcinoma(GC)samples(36/40)wassignificantlyhigherthanthatobservedingastritis(19/
45) or normal samples (7/13) (P,0.01). Extensive clone sequencing of these sMSP products showed that the density of
methylated-CpGsinp16CpGislandsincreasedgraduallyalongwiththeseverityofpathologicalchangesingastrictissues.In
gastritislesionsthemethylationwasfrequentlyobservedintheregioncorrespondingtotheexon-1coding-nucleosome
and the 59UTR-nucleosome; the methylation was further extended to the region corresponding to the promoter-
nucleosome in GC samples. Only few methylated-CpG sites were randomly detected within p16 CpG islands in normal
tissues.Thesignificantlyinversedrelationshipbetweenthep16exon-1methylationanditstranscriptionwasobservedinGC
samples.Anexactp16promoter-specific83bp-MSPassayconfirmstheresultofsMSP(33/55vs.1/6,P,0.01).Inaddition,
p16methylationinchronicgastritislesionssignificantlycorrelatedwithH.pyloriinfection;however,suchcorrelationwasnot
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