Aberrant promoter methylation profiles of tumor suppressor genes in hepatocellular carcinoma.

  • Yang B
  • Guo M
  • Herman J
 et al. 
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Abstract

Hepatocellular carcinoma {(HCC)} is one of the most fatal human malignancies, but the molecular mechanisms of hepatocarcinogenesis remain unclear. Although p53 mutations are frequently observed in Asian {HCC,} it is not a common event in Western {HCC.} Recent studies suggest that tumor suppressor genes {(TSGs)} can also be silenced through epigenetic disruption, such as promoter {CpG} island methylation, during carcinogenesis. To further understand the molecular mechanism of hepatocarcinogenesis, we have investigated the promoter methylation status of nine {TSGs} {(SOCS-1,} {GSTP,} {APC,} E-cadherin, {RAR-beta,} p14, p15, p16, and p73) in 51 cases of {HCC} using methylation-specific polymerase chain reaction. We found that 82% of {HCCs} had methylation of at least one {TSG} promoter. The most frequently methylated {TSGs} in {HCC} were: {SOCS-1} (65%), {GSTP} (54%), {APC} (53%), E-cadherin (49%), and p15 (49%). Methylation of {SOCS-1,} {GSTP,} {APC,} E-cadherin, and p15 was more frequent in {HCC} than in nontumor liver {(P} < 0.05). Methylation of {SOCS-1,} {GSTP,} and p15 was also significantly more frequent in {HCC} than cirrhotic liver {(P} < 0.05). Although methylation of one or two genes could be seen in both nontumor and cirrhotic livers, 53% of the {HCC} cases had three or more {TSG} promoters methylated, in comparison to 0% in nontumor liver and 13% in cirrhosis {(P} = 0.001). Methylation of {SOCS-1,} {APC,} and p15 was more frequently seen in hepatitis C virus-positive {HCC} than hepatitis C virus/hepatitis B virus-negative {HCC.} Our data suggest that promoter hypermethylation of {TSGs} is a common event in {HCC} and may play an important role in hepatocarcinogenesis.

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Authors

  • Bin Yang

  • Mingzhou Guo

  • James Herman

  • Douglas Clark

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