Abstract 394: TET1, which act as an tumor suppressor gene, is suppressed by DNA hypermethylation in gastric cancer

5-hydromethylcytosine (5hmC) is a hydroxmethylated form of DNA cytosine catalyzed by TET proteins. Recently, it was reported that aberrant regulation of 5hmC is associated with many cancers such as breast cancer, glioma, leukemia and melanoma. In this study, we examined the status of 5hmC and the role of TET1, which converts 5mC to 5hmC, in gastric cancer. Dot blot and ELISA assay results revealed global loss of 5hmC level in gastric cancer, and that decreased TET1 expression was associated with decreased 5hmC levels. Importantly, in gastric cancer patients, TET1-low group had advanced metastasis and poor survival compared with TET1-high group. To understand the mechanisms of TET1 suppression in gastric cancer, we performed pyrosequencing in 80 paired normal and tumors samples from gastric cancer patients, and found that the promoter region of TET1 was hypermethylated in tumors than adjacent normal tissues. Treating AGS cells with 5-Aza-2′deoxycytidine (Aza-dC) restored the expression of TET1. Transient transfection of in vitro transcribed TET1 mRNA into AGS cells significantly reduced the growth of AGS cells. In summary, our results showed that DNA methylation is responsible for the suppression of TET1 which has a tumor suppressor role in gastric cancer Citation Format: Jong-Lyul Park, Oh-Hyung Kwon, Kyu Sang Song, Seon-Young Kim, Yong Sung Kim. TET1, which act as an tumor suppressor gene, is suppressed by DNA hypermethylation in gastric cancer. [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 394. doi:10.1158/1538-7445.AM2014-394