Purpose: CpG island methylator phenotype (CIMP) involves hypermethylation targeted toward the promoters of multiple genes. To gain insight into the role of epigenetic aberration of tumorrelated genes in hepatocarcinogenesis, we determined a hypermethylation profile in hepatocellular carcinoma (HCC). Experimental Design: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 a-fetoprotein (AFP) level (P = 0.017). CIMP+ was more frequent in HCC with AFP z 30 Ag/L than those with AFP < 30Ag/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.

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Background: Aberrant promoter methylation is an important mechanism for gene silencing. Aims: To evaluate the promoter methylation status of p300 gene in patients with oesophageal squamous cell carcinoma (OSCC). Methods: The methylation status of p300 promoter was analysed by methylation-specific PCR (MSP) in 50 OSCC tissues and the matching non-cancerous tissues. Oesophageal cancer cell lines (ECa-109 and TE-10) were treated with the demethylation agent 5-aza-29-deoxycytidine (5-Aza-CdR), and p300 mRNA expression was detected by RT-PCR. Results: p300 methylation was found in 42% (21/50) of the OSCC tissues, but in only 20% (10/50) of the corresponding non-cancerous tissues (p = 0.017). In OSCC samples, 65% of those with deep tumour invasion (adventitia) and 63% samples with metastasis revealed p300 promoter methylation (p,0.05). p300 mRNA expression was observed in 19.0% (4/21) of methylated tumours and 58.6% (17/29) of unmethylated tumours (p = 0.005). In addition, p300 mRNA expression was observed in 40% (4/10) of methylated nonneoplastic tissues and 87.5% (35/40) of unmethylated non-tumours (p = 0.001). The demethylation caused by 5-Aza-CdR increased the p300 mRNA expression levels in oesophageal cancer cell lines. Conclusions: p300 transcription silenced by promoter hypermethylation could play a role in the pathogenesis of oesophageal squamous cell carcinoma.

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