Molecular mechanisms of DNA methylation alterations in precancerous conditions

2014 Fiscal Year Final Research Report

• Project/Area Number: 23390096
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: National Cancer Center Japan
• Principal Investigator: KANAI Yae 独立行政法人国立がん研究センター, 研究所, 分野長 (00260315)
• Co-Investigator(Kenkyū-buntansha): ARAI Eri 国立研究開発法人国立がん研究センター研究所, 分子病理分野, 主任研究員 (40446547)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: DNAメチル化 / ヒストン修飾 / 前がん状態 / 腎がん / 肝がん

Outline of Final Research Achievements

The aim of this study was to understand molecular mechanisms of DNA methylation alterations in precancerous conditions. Multi-layer omics abnormalities of histone methyltransferase, histone demethylase and histone acetyltransferase were observed in CpG islands methylator phenotype-positive renal cell carcinomas. H3K4me3 and H3K27Ac modifications preceded DNA methylation alterations at the chronic hepatitis and liver cirrhosis stages which are widely considered to be precancerous conditions for hepatocellular carcinomas. Histone modification alterations based on abnormalities of histone modification enzymes may be fixed due to DNA methylation alterations during multistage carcinogenesis and may determine aggressiveness of cancers.

Free Research Field

腫瘍病理学、発がんエピジェネティクス