Abstract
Abstract Objective: DNA methylation is a fundamental epigenetic process that modulates gene expression. Cancer cells exhibit two types of DNA methylation alterations: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Although the base 5-methylcytosine (5mc) and the DNA methyltransferase (DNMT) family of enzymes that catalyze DNA methylation are well-studied, the mechanisms of DNA demethylation are poorly understood. The Ten-eleven translocation (Tet) family of enzymes (Tet1, Tet2, and Tet3) has been implicated in DNA demethylation. These enzymes possess the dioxygenase activity and convert 5-mC to 5-hydroxymethylcytosine (5-hmC). Frequent Tet mutational inactivation or reduction has been reported to associate with decreased 5-hmC levels in various types of myeloid leukemia and melanoma. However, the status of 5hmC and Tet expression in esophageal squamous cell carcinoma (ESCC) remains still unknown. Method: We analyzed the 5-hmC status in DNA from ESCC frozen tissues utilizing the ELISA test, and 5-hmC expression was evaluated by immunohistochemistry. We next examined the expression levels of Tet family mRNA in both normal and tumor tissues by RT-qPCR. Results: 5-hmC level was significantly lower in ESCC than in paired normal tissue in ELISA test (n=33, P<0.0001). The similar result was observed in immunohistochemistry. We found that the Tet2 mRNA expression was significantly lower in ESCCs than paired normal tissues (n=32, P<0.0001). The expression level of Tet2 mRNA was significantly associated with the 5hmC status (n=31, r=0.54, P=0.0085). Finally, 5-hmC status did not correlate with overall survival (P = 0.65). Conclusion: The 5hmC expression was decreased in ESCC tissues, and was associated with Tet2 expression level, suggesting that 5hmC and Tet2 might play a crucial role in the development of ESCCs. Citation Format: Asuka Murata, Yoshifumi Baba, Ryuichi Karashima, Satoshi Ida, Yu Imamura, Takatsugu Ishimoto, Shiro Iwagami, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Hideo Baba. Tet family proteins and 5-hydroxymethylcytosine in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 420. doi:10.1158/1538-7445.AM2014-420
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