title: CpG island methylator phenotype association with elevated serum alpha-fetoprotein level in hepatocellular carcinoma.
abstract: OBJECTIVE
  CpG island methylator phenotype (CIMP) involves hypermethylation targeted toward the promoters of multiple genes. To gain insight into the role of epigenetic aberration of tumor-related genes in hepatocarcinogenesis, we determined a hypermethylation profile in hepatocellular carcinoma (HCC).
  
  
  METHODS
  We examined the promoter methylation status of nine genes in 50 HCCs, 50 paired nontumor tissues, and 6 normal liver tissues by methylation-specific PCR. CIMP+ was defined as having five genes that are concordantly methylated.
  
  
  RESULTS
  The frequency of promoter methylation of nine genes in 50 HCCs varied from 10% in P53 to 94% in c-Myc. The methylation status of P14, P15, P16, ER, RASSF1A, WT1, and c-Myc was significantly correlated with HCC and nontumor tissues (P<0.05). Hypermethylation of one or more genes was found in 96% of HCC. CIMP was more frequent in HCC than in nontumor tissues (70% and 12%, P<0.001). There is a significant association between CIMP and methylation of P14, P15, P16, ER, RSAAF1A, and WT1 (P<0.05) and serum alpha-fetoprotein (AFP) level (P=0.017). CIMP+ was more frequent in HCC with AFP>or=30 microg/L than those with AFP<30 microg/L (P=0.005). In addition, the promoter hypermethylation of P15 and P16 was associated with elevated serum AFP levels in 35 HCC samples with CIMP+ (P<0.05).
  
  
  CONCLUSIONS
  Positive correlation of CIMP and AFP levels in HCC suggests that CIMP can serve as a molecular marker of late-stage HCC development.
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Changsong
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhengyou
authors.initials: Z
authors.lastname: Li
authors.forename: Yue
authors.initials: Y
authors.lastname: Cheng
authors.forename: Fengqi
authors.initials: F
authors.lastname: Jia
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.forename: Mengchao
authors.initials: M
authors.lastname: Wu
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011401:Promoter Regions, Genetic; D000509:alpha-Fetoproteins / Q000096:biosynthesis*
chemical_list: D017931:DNA Primers; D000509:alpha-Fetoproteins