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Promoter Hypermethylation of RASSF1A in Esophageal Squamous Cell Carcinoma¹

Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, Pennsylvania 19107 [T. K., F. T., S. Y., A. M., H. A., C. M. C.], and Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu 874-0838, Japan [M. M.]

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.

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