Elucidation of the gliomagenesis by comprehensive epigenetic analysis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17972
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Kyushu University
• Principal Investigator: Sangatsuda Yuhei 九州大学, 大学病院, 助教 (00848640)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: グリオーマ / DNAメチル化 / エピゲノム / H3F3A / ヒストン

Outline of Final Research Achievements

Epigenetic analysis of H3F3A gene G34 mutant glioma was carried out, focusing on whole-genome DNA methylation analysis using PBAT method. We identified that the G34 mutant group exhibited genome-wide CpG hypomethylation and CpG island (CGI) hypermethylation, and that CGI hypermethylation near telomeres was relatively attenuated. G34-mutated glioma-specific methylation signals were detected by independent component analysis and they are shared in bone tumors with the same mutation. ChIP-seq suggested that this signal was associated with the localization of the G34-mutated histone H3.3, and that this signal was partially reversible by knocking out the mutation in cell lines.

Free Research Field

脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究で得られたデータは本邦最初のグリオーマの全ゲノム的メチル化データであり、G34変異グリオーマについて世界最初のものとなった。これらのデータセットはJapanese Genotype-phenotype Archiveへデータ登録しており、後発研究に利用可能である。今回得られた知見はH3F3A遺伝子G34変異によって生じた変異ヒストンの局在の特徴やDNAメチル化に及ぼす影響を解明する一助となり、将来的に同変異をターゲットとした治療法の開発につながることが期待される。