Stratification of gastric cancer and identification of molecular mechanism of gastric tumorigenesis based on aberrant DNA methylation profile

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05412
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Chiba University
• Principal Investigator: Kaneda Atsushi 千葉大学, 大学院医学研究院, 教授 (10313024)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: がん / エピゲノム

Outline of Final Research Achievements

We conducted genome-wide DNA methylation analysis of clinical gastric cancer samples to classify gastric cancer into several molecular subtypes, and we also conducted exon-sequencing analysis to identify genetic mutations specifically observed in each subtype. As for high-methylation gastric cancer subtypes, we clarified molecular mechanisms of gastric cancer through synergy of genetic mutations and aberrant DNA methylation. Moreover, we analyzed the mechanisms to induce aberrant epigenomic aberrations in gastric epithelial cells. We infected Epstein-Barr virus to gastric epithelial cells in vitro, and showed that EBV infection induced extensive DNA hypermethylation within four weeks genomewidely, and repression of TET2 was one of the molecular mechanisms for DNA methylation induction.

Free Research Field

消化器外科、エピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

癌は我が国において生涯のうちに1/2の者が罹患し1/3の者の死因となる疾患であり、網羅的解析により癌の原因を明らかにすることは学術的にも、また新たな治療方法を構築して社会的に貢献する意味でも大変重要である。その中でも胃癌は重要な癌死要因の１つであり、胃癌における分子異常を詳細に同定し、その中から胃発癌に重要な分子異常を同定したこと、またどのようにその分子異常が蓄積したのかその原因の一端を明らかにしたことは、発癌機構を理解する上で学術的にも、また今後新たな胃癌治療法を確立する上でも、意義のある成果をあげた。