Demethylation alteration induced by H. Pylori infection and its relation to chromosomal instability

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10515
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Jichi Medical University
• Principal Investigator: SAITO Masaaki 自治医科大学, 医学部, 講師 (00382911)
• Co-Investigator(Kenkyū-buntansha): 鈴木 浩一 自治医科大学, 医学部, 准教授 (70332369) ; 力山 敏樹 自治医科大学, 医学部, 教授 (80343060)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: セントロメア / 脱メチル化異常 / 染色体不安定性 / Satellite RNA

Outline of Final Research Achievements

We previously reported that overexpression of satellite alpha transcript (SAT) facilitates chromosomal instability, which is involved in the development of multiple tumors in patients with colorectal. The centromere consists of satellite alpha repetitive sequences, which are ideal targets for DNA hypomethylation, resulting in the overexpression of SAT. In this study, we elucidated the significance of DNA demethylation of SAT in the development of multiple tumors in patients with gastric cancer. Relative demethylation level of SAT was calculated from 103 gastric patients. Patients with multiple gastric cancer (n=20) showed higher demethylation levels than those in patients with single cancer (n=83, P<0.001). Additionally, multivariate analysis revealed that the demethylation level of SAT was a significant factor for predicting multiple gastric cancer (P=0.008). Our data indicated that DNA demethylation of SAT was involved in the development of multiple gastric cancer.

Free Research Field

腫瘍外科学

Academic Significance and Societal Importance of the Research Achievements

本研究によってセントロメア領域の脱メチル化異常による発癌の機序として、Satellite transcriptの転写が亢進し、RNAi機構やセントロメア蛋白の発現が助長され、染色体不安定性が誘導される事が考えられた。この経路にはp53蛋白の変異は関与しておらず、古典的な分化型胃癌の発癌過程とは異なるSatelliteαの脱メチル化を介する新たな発癌経路の発見の糸口となる事が期待される。