Elucidation of the gliomagenesis by comprehensive epigenetic analysis
Project/Area Number |
20K17972
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56010:Neurosurgery-related
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Research Institution | Kyushu University |
Principal Investigator |
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | グリオーマ / DNAメチル化 / エピゲノム / H3F3A / ヒストン / H3F3A遺伝子 / 次世代シークエンス / PBAT法 |
Outline of Research at the Start |
次世代シーケンサー技術の飛躍的な進歩により、癌をはじめ様々な生体現象の理解が進むようになった。Post-bisulfite adapter tagging (PBAT)法は高精度な全ゲノム的DNAメチル化解析 (Whole-genome bisulfite sequencing: WGBS)の新たな手法である。我々は最近このPBAT法を改良することで、より高効率に良質なメチロームデータを得ることに成功した。本研究では改良型PBAT法を用いたWGBSを中心に、臨床検体を用いたエピゲノムおよびトランスクリプトーム解析を行うことでグリオーマの未知の病態解明および新規治療アプローチの開発に繋がる知見を獲得することを目的とする。
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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.
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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。
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Report
(4 results)
Research Products
(4 results)
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[Journal Article] Base-resolution methylomes of gliomas bearing histone H3.3 mutations reveal a G34 mutant-specific signature shared with bone tumors2020
Author(s)
Yuhei Sangatsuda, Fumihito Miura, Hiromitsu Araki, Masahiro Mizoguchi, Nobuhiro Hata, Daisuke Kuga, Ryusuke Hatae, Yojiro Akagi, Takeo Amemiya, Yutaka Fujioka, Yasuhito Arai, Akihiko Yoshida, Tatsuhiro Shibata, Koji Yoshimoto, Koji Iihara & Takashi Ito
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Journal Title
Scientific Reports
Volume: 10
Issue: 1
Pages: 16162-16162
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Base-resolution methylomes of gliomas bearing histone H3.3 mutations reveal a G34 mutant-specific signature shared with bone tumors2020
Author(s)
Yuhei Sangatsuda, Fumihito Miura, Hiromitsu Araki, Masahiro Mizoguchi, Nobuhiro Hata, Daisuke Kuga, Ryusuke Hatae, Yojiro Akagi, Takeo Amemiya, Yutaka Fujioka, Yasuhito Arai, Akihiko Yoshida, Tatsuhiro Shibata, Koji Yoshimoto, Koji Iihara & Takashi Ito
Organizer
The 19th International Symposium on Pediatric Neuro-Oncology
Related Report
Int'l Joint Research