結腸直腸がんの進化におけるフェノタイプの可塑性と遺伝的制御

Jacob Househam^1,2, Timon Heide^1,3, George D Cresswell¹

¹Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.

Nature

|October 26, 2022

まとめ

大腸がん (CRC) のほとんどの遺伝的変化は遺伝子発現や腫瘍の進化に影響を与えない. 代わりにトランスクリプションの可塑性つまり遺伝子の活動を変える能力は腫瘍内で広く見られます

科学分野:

腫瘍学
ゲノミクス
分子生物学

背景:

腫瘍内多様性は,遺伝的および表遺伝的多様性,および転写的可塑性から生じる.
これらのプロセスの腫瘍進化への具体的な貢献は完全に理解されていません.

研究の目的:

結腸直腸がん (CRC) の遺伝的祖先,遺伝子発現,サブクローン進化の相互作用を調査する.
腫瘍内遺伝子変異が表型特性と腫瘍の進行にどの程度影響するかを決定する.

主な方法:

空間的に解明されたペア化された全ゲノムとトランスクリプトームの結腸直腸がん (CRC) サンプル.
遺伝子発現の遺伝子制御を特定するための体表現定量特征ロシ (eQTL) 分析.
空間パターニングとサブクローン選択を分析するために,腫瘍の系統を計算的に推論する.

主要な成果:

腫瘍内遺伝的祖先は,CRCにおける遺伝子発現とサブクローン進化をめったに影響しません.
内腫瘍の遺伝子発現の変異のほとんどは,遺伝的ではなく,プラスティックです.
CRC腫瘍内のほとんどの遺伝的変異は,限られた現象的結果を持ち,トランスクリプションの可塑性は一般的です.

結論:

転写性可塑性は,大腸がん (CRC) 腫瘍の表型を形作る上で遺伝的変異よりも重要な役割を果たします.
これらのダイナミクスを理解することは,標的療法を開発し,CRCにおける治療反応を予測するために不可欠です.

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