DNA甲基化转移酶 DNMT2含有DNA甲基化活性区域，但主要甲基化tRNA。文献报道其分子多态性导致H101T突变并与胃癌发病率显著相关，但是二者关联的分子机制国际国内尚无报道；此外DNMT2甲基化tRNA机制及其是否介导胃癌的发生发展也不清楚。我们将通过生物化学与分子生物学等技术，研究野生型和H101T突变型DNMT2对tRNA底物甲基化作用的差别及其对细胞癌化的影响，并通过分析在正常与癌变细胞、正常与癌变小鼠及临床胃癌病人癌变组织中DNMT2表达水平、其甲基化tRNA产物水平及与其结合的蛋白和/或核酸，并观测这些指标对应激状态的变化，来探讨DNMT2在胃癌发病中的分子机制。研究结果将为胃癌的早期诊断和干预手段提供新的潜在的靶点和思路，并为抗胃癌药物的研制提供新的线索和理论依据。

DNMT2，a member of DNA methyltransferase family, while containing DNA methyltransferase domain, mainly methylates eukaryotic tRNA. One of DNMT2 polymorphisms, which led to H101T mutation, was found to be significantly associated with susceptibility of gastric cancer. So far, the detailed mechanisms of DNMT2 association with gastric cancer has never been studied. It is unclear how DNMT2 recognizes tRNA substrates and whether DNMT2 methylation mediates the onset and progression of gastric cancer. In this study, on one hand,we aim to address the methylation mechanisms of wild type (WT) DNMT2 and its H101T mutant using kinetic approach，and to examine the effect on cell carcinogenesis by overexpressing the WT DNMT2 and H101T mutant in cell culture. On the other hand, we propose to search DNMT2 binding partners and to measure the level of DNMT2 expression and tRNA methlylaion under normal and cancerous conditions, using cell lines, mouse tissue and cancer tissue from gastric cancer patients. Additionally, we intend to monitor the changes of DNMT2 binding partner and its expression, as well as tRNA methylation in response to stress stimulus.The proposed work will uncover the molecular details relating DNMT2 to gastric cancer, and will provide a new potential target, strategy and theoretical basis for early cancer detection and prevention as well as anticancer drug development.