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Epigenetic silencing of tumor suppressor genes in neoplasia has been recognized as a common mechanism of cancer development. Genes which exhibit frequent cancer-specific methylation may have tumor suppressive activities and hold value as biomarkers for cancer diagnosis. Pharmacological unmasking in esophageal squamous cell carcinoma (ESCC) cell lines uncovered the neurofilament heavy chain (NEFH) gene as a candidate methylated gene. NEFH expression was silenced in ESCC cell lines and reactivated by the demethylating agent, 5-aza-2’-deoxycytidine. Quantitative methylation-specific PCR detected NEFH promoter hypermethylation in 34/70 (48.5%) primary human ESCC and absent or minimal levels in normal corresponding tissues. Moreover, overexpression of NEFH in ESCC cell lines effectively inhibited the formation of cell colonies (44% compared to control vector). NEFH silencing may, thus, provide a selective growth advantage during ESCC tumorigenesis. Furthermore, NEFH methylation shows promise as a biomarker for ESCC due to its common occurrence and high cancer cell specificity.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA