Genome-wide DNA methylation analysis in dogs: Identification of tumor-specific DNA methylation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K05964
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Hokkaido University
• Principal Investigator: Yamazaki Jumpei 北海道大学, 獣医学研究院, 特任准教授 (20732902)
• Co-Investigator(Kenkyū-buntansha): 市居 修 北海道大学, 獣医学研究院, 准教授 (60547769)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: エピジェネティクス / DNAメチル化 / 腫瘍

Outline of Final Research Achievements

Genome-wide analysis of DNA methylation by next-generation sequencing for 16 canine somatic tissues, 28 malignant melanomas with normal mucosae, and 12 hepatocellular carcinomas with normal liver cells with or without steroid treatment were performed to obtain quantitative DNA methylation levels of 100,000-150,000 CpG sites in the dog genome.
We found that the normal tissue types were clearly defined by principal component analysis and hierarchical clustering analysis with DNA methylome. DNA methylation patterns were clearly different between malignant melanoma and normal mucosae. Same is true between HCC and normal liver cells. These findings suggest molecular subtypes defined by aberrant DNA methylation occurred in these tumor patients, which have never been elucidated in the clinical settings.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

これまで研究されてきたイヌの腫瘍疾患におけるDNAメチル化の異常は、かなり局所的な解析によるものにとどまっていたが、本研究によってその解析範囲が大幅に改善されたことで広範な異常が存在することが明らかとなり、イヌの腫瘍疾患における分子生物学的なメカニズムの理解が刷新されたことは学術的意義が深い。
また本研究の成果による、獣医診療におけるバイオマーカー樹立や新規治療法の策定などの臨床応用への可能性が示唆された点においては、コンパニオンアニマルとしてのイヌ、およびともに暮らす人間のより良い暮らしといった社会的意義につながる。