マウスの腫瘍の誘導は,ゲノム性低メチル化による
François Gaudet1, J Graeme Hodgson, Amir Eden
1Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
まとめ
エピジェネティックの変化であるDNA低甲基化は,がんの発症に因果的な役割を果たします. マウスのDNAメチルトランスフェラーゼ1 (Dnmt1) の減少は,全ゲノムにわたる低メチル化および攻撃的なT細胞リンパ腫を引き起こした.
科学分野:
- エピジェネティクス エピジェネティクス
- がん生物学 がん生物学
- 遺伝学 遺伝学とは
背景:
- 全ゲノムにわたるDNA低メチル化は,ヒトの癌で観察されています.
- 腫瘍発生の原因または結果としてのその役割は不明である.
研究 の 目的:
- 腫瘍形成におけるDNA低甲基化の因果的役割を調査する.
- 低メチル化と染色体の不安定性との関連を調査する.
主な方法:
- 低形状DNAメチルトランスファーゼ1 (Dnmt1) アレルを持つマウスを生成した.
- Dnmt1の発現が野生型のレベルの10%に低下し,全ゲノムにわたる低メチル化を引き起こします.
主要な成果:
- ミュータントマウスは,誕生時にを呈していた.
- 4〜8ヶ月の年齢までに攻撃的なT細胞リンパ腫を発症した.
- リンパ腫は15染色体トリソミーの高い頻度を示した.
結論:
- DNA低甲基化は,がんの発症に因果的な役割を果たします.
- 低メチル化は,染色体不安定性を誘発することによって腫瘍形成を促進する可能性があります.
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