Dysregulation of DNA demethylation in the first step of pancreatic tumorigenesis and its molecular mechanisms.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07372
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Kobe University
• Principal Investigator: Fujikura Kohei 神戸大学, 医学研究科, 医学研究員 (50773751)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 膵癌 / 前がん病変 / メチル化

Outline of Final Research Achievements

5-hydroxymethylcytosine (5hmC), an intermediate product of DNA demethylation, was stained for pancreatic cancer, four precancerous lesions (PanIN, IPMN, MCN, IOPN), and normal pancreatic duct epithelium. The results demonstrated a decreased signal of 5hmC in almost all lesions. Given that the TET gene is essential for the synthesis of 5-hydroxymethylcytosine, we proceeded to stain TET1. The result showed a similarly aberrant decrease in expression, and a clear correlation between the two was also observed. A comprehensive analysis revealed that demethylation is dysregulated in early pancreatic tumorigenesis.

Free Research Field

病理診断

Academic Significance and Societal Importance of the Research Achievements

TET1の低下が5-ヒドロキシメチルシトシンの低下の原因である可能性が示唆された。脱メチル化が初期の膵腫瘍においても異常を来していることを包括的に解析し明らかにしたのは、本研究が初めてである。将来的にTET1が引き起こす脱メチル化異常は膵癌とその全眼病右辺の治療対象となりうる可能性が示唆された。