Promoter hypermethylation of RASSF1A in esophageal squamous cell carcinoma.

PURPOSE The RAS association domain family 1A (RASSF1A) gene, a candidate tumor suppressor gene, is frequently inactivated by hypermethylation of its promoter region in several human cancers. The aim of this study was to evaluate the promoter methylation status of the RASSF1A in esophageal squamous cell carcinoma. EXPERIMENTAL DESIGN We analyzed the methylation status of RASSF1A promoter by methylation-specific PCR in 23 esophageal squamous cell carcinoma cell lines and 48 primary tumors. RESULTS Hypermethylation of RASSF1A was found in 74% of cell lines and 52% of primary tumors. The presence of hypermethylation was statistically associated with loss of RASSF1A mRNA expression in both cell lines (P = 0.007) and primary tumors (P = 0.003). There was a statistically significant correlation between the presence of hypermethylation and tumor stage (P = 0.009). CONCLUSIONS Our findings suggest that epigenetic silencing of RASSF1A gene expression by promoter hypermethylation could play an important role in primary esophageal squamous cell carcinogenesis.