title: Progression of hypermethylation of the p16(INK4A) gene from normal liver to nontumorous liver and hepatocellular carcinoma: an evaluation using quantitative PCR analysis.
abstract: The aim of this study was to determine to what extent hypermethylation of the p16(INK4A) (p16) gene promoter is increased in nontumorous liver tissues compared with in normal liver, using two quantitative methylation-specific polymerase chain reaction (MS-PCR) methods and a bisulfite sequencing method. Methylation of the p16 gene was detected more frequently in nontumorous liver than in normal liver using the TaqMan PCR method. Methylation indices also were significantly higher in nontumorous than in normal liver. However, the bisulfite sequencing method did not detect significantly more methylation of the p16 gene in nontumorous than normal liver, nor was there a significant difference in the level of p16 mRNA. There may be a greater proportion of cells which contain methylated p16 in nontumorous than in normal liver. However, the difference was so small that the functional relevance to hepatocarcinogenesis remains elusive.
authors.affiliation: Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences of Niigata University, 1-754, Asahimachi-Dori, Niigata-city, 951-8122, Japan.
authors.forename: So
authors.initials: S
authors.lastname: Kurita
authors.forename: Shogo
authors.initials: S
authors.lastname: Ohkoshi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yano
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Kenta
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yo-hei
authors.initials: YH
authors.lastname: Aoki
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Wakai
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Shirai
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ichida
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Aoyagi
mesh_terms: D000483:Alleles; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D012333:RNA, Messenger