環境 エージェント の 変異 特徴 の 総集
Jill E Kucab1, Xueqing Zou2, Sandro Morganella3
1Department of Analytical, Environmental and Forensic Sciences, MRC-PHE Centre for Environment and Health, King's College London, 150 Stamford Street, London SE1 9NH, UK.
Cell
|April 16, 2019
まとめ
環境の発がん物質はヒトの幹細胞に 独特のDNA変異パターンを引き起こします この研究は特定の変異のサインを特定し 細胞修復メカニズムと 人間のDNAの環境への直接的な脆弱性を明らかにします
科学分野:
- ゲノミクス
- 環境 健康
- 癌 研究
背景:
- ヒト腫瘍の全ゲノム配列解析 (WGS) は,がんの発生と関連した変異パターンを明らかにしています.
- 癌を引き起こす物質を特定するには 環境への曝露を理解することが重要です
研究 の 目的:
- 環境から発がん物質に曝されたヒトの幹細胞の変異シグネチャーを調査する.
- 変異体によるダメージの解消に関与するDNA修復経路の特徴づけ
主な方法:
- 324種類のヒト誘発性多能幹細胞の全ゲノムシーケンシング (WGS)
- 幹細胞を79の既知のまたは疑われる環境発がん物質に曝露する.
- 変異シグネチャーの分析, 置換,二重置換,挿入/削除 (インデル) を含む.
主要な成果:
- 41の発がん物質は 特徴的な置換変異シグネチャを誘発し,その中にはヒトの腫瘍に似たものもあります
- 6人のエージェントがダブルシグネチャーシグネチャー,8人がインデルシグネチャーシグネチャーシグネチャー
- 変異非対称性分析は機能的不一致と転写結合DNA修復経路を確認した.
結論:
- 環境の変異因子は様々な修復経路を介してヒトの幹細胞に様々な変異シグネチャーを誘発する.
- この要約は,がんの病因に関する環境要因を調査するのに役立ちます.
- 人間の幹細胞のDNAは 直接的に環境への影響を受けやすいのです
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