肺がんと転移におけるゲノム・トランスクリプトミックの進化
Carlos Martínez-Ruiz1,2, James R M Black1,2, Clare Puttick1,2,3
1Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Nature
|April 12, 2023
まとめ
肺内腫瘍の異質性は肺がんの進化と治療抵抗性を左右する. この研究は,トランスクリプトーム
科学分野:
- 腫瘍学
- ゲノミクス
- トランスクリプトミクス
背景:
- 腫瘍内異質性 (ITH) は肺がんの進行,免疫回避,および治療抵抗の主要な要因です.
- ITHの分子基盤を理解することは 効果的な肺がん治療の開発に不可欠です
研究 の 目的:
- 非小細胞肺がん (NSCLC) の内腫瘍のトランスクリプトミア多様性を調査する.
- 遺伝子発現,ITH,腫瘍の進化の関係を探求する.
- 癌の進行と転移に寄与するRNAベースのメカニズムを特定する.
主な方法:
- TRACERx研究からの354のNSCLC腫瘍と96の隣接する正常組織のペアリングされた全エクソームとRNAシーケンシング.
- 947の腫瘍領域 (原発性および転移性) を分析して,トランスクリプトミックの変化を評価する.
- ゲノムとトランスクリプトミックのデータを転移の可能性と結びつけるための機械学習の適用.
主要な成果:
- トランスクリプトームはNSCLCにおける表型変異とITHに有意に寄与する.
- 複製数の変化とはしばしば独立するアレル特異的発現は,エピジェノミック機能不全とゲノム-トランスクリプトミックの並列進化と関連している.
- 単基RNA置換シグネチャーはADARとAPOBEC3Aの活性を示し,進行中のAPOBECの活性を示しています.
- メタスタシス発生の可能性は,変異の進化的文脈と,原発性腫瘍の増殖に関連しています.
結論:
- ゲノムとトランスクリプトームの相互作用は,ITHの形成と肺がんの進化を促す上で極めて重要です.
- トランスクリプトミックの多様性とRNA編集は,肺がんの進行と治療抵抗性において重要な役割を果たします.
- ゲノムとトランスクリプトミックの分析は,転移のメカニズムと潜在的な治療標的の洞察を提供します.
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