大腸がんにおけるゲノムとエピゲノムの共進化

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

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

Nature

|October 26, 2022

まとめ

この研究は結腸直腸がんをマッピングしています.

科学分野:

ゲノミクス
エピジェネティクス
癌生物学

背景:

結腸直腸の悪性腫瘍は,癌による死亡の重要な原因である.
ゲノム研究だけでは癌の発生を完全に説明できません
ゲノムとエピジェノムの相互作用を理解することは極めて重要です

研究の目的:

結腸直腸腫瘍におけるゲノムとエピジェノムの共同進化を調査する.
単一クローンの解像度で遺伝的および表遺伝的異質性を分析する.
結腸直腸腫瘍形成における表遺伝的変異の役割を調査する.

主な方法:

個々の結腸腺の空間的多分子プロファイリング
30種類の原発がんと8種類のアデノマから 1,370個のサンプルを採取した.
クロマチンのアクセシビリティ,全ゲノム,全トランスクリプトームのデータ生成

主要な成果:

染色体改変遺伝子におけるDNA変異の陽性選択を特定した.
癌の誘発因子の規制領域を含む,再発性体内クロマチンのアクセシビリティの変化を発見した.
転写因子結合アクセシビリティ (CTCF,SOX,HOX) とインターフェロンシグナル伝達における全ゲノムの変化を観察した.
染色体アクセシビリティの変化の遺伝性が示され,腺腫と癌を区別する.
エピゲノムがDNA変異の蓄積に影響を及ぼすことを示した.

結論:

結腸直腸がんにおける遺伝的および表遺伝的異質性の包括的な地図を提供します.
腫瘍の発達に遺伝子の関与を強調しています
癌の進行におけるエピジェノームとゲノムの双方向関係を示唆している.
大腸がんの生物学に関する根本的な洞察を提示しています

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