Epigenetic alterations and tumor heterogeneity in gastric cancers

2015 Fiscal Year Final Research Report

• Project/Area Number: 24590444
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: AKIYAMA Yoshimitsu 東京医科歯科大学, 医歯(薬)学総合研究科, 講師 (80262187)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: メチル化 / ヒストン / 胃がん / エピジェネティクス / 組織内多様性

Outline of Final Research Achievements

In this study, we focused on the relationship between epigenetic changes of genes and tumor heterogeneity of gastric cancers (GCs). Expression of SET7/9, a histone mono-methyltransferase, was frequently reduced in primary GCs, some of which expression patterns were distinct within a GC tissue. SET7/9 regulated several differentiation-related gene expression and had tumor suppressive functions. In addition, several mouse GC cell lines showing distinct Twist1 expression pattern were established from the p53/E-cadherin double knockout mice. Twist1 expression was epigenetically regulated by DNA methylation, histone modification and binding of transcription factor Sp1 in these mouse GC cells. Our data suggest that tumor heterogeneity of GCs may be related to epigenetic alterations.

Free Research Field

医歯薬学 (分子病理学, 分子腫瘍学)