浸透した病変分離が癌のゲノム進化を形作る

Sarah J Aitken^1,2,3, Craig J Anderson⁴, Frances Connor¹

¹Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.

Nature

|June 26, 2020

まとめ

ほとんどのDNA病変は細胞分裂にわたって持続し,染色体規模の変異パターンにつながります. これは突然変異が遺伝的多様性を生み出しがんゲノム進化に影響する理由を説明しています

科学分野:

遺伝学
癌生物学
ゲノミクス

背景:

癌は遺伝子変異とクローン拡大によって発生します
DNAの損傷の運命と細胞サイクルにおける突然変異パターンへの影響は完全に理解されていません.

研究の目的:

複数の細胞サイクルにわたる変異性DNA損傷の運命を調査する
修復されていないDNAの損傷が癌の変異パターンと遺伝的多様性に寄与する仕組みを理解するためです

主な方法:

ミュタゲン誘発のマウス肝臓腫瘍の分析
DNA病変の分離とその後の変異の特徴
持続的な病変の間のDNA複製の検査

主要な成果:

ほとんどの変異性DNAの損傷は単細胞サイクルで修復されず,子細胞に分離する.
この分離は変異の染色体スケール段階化につながる.
持続的な病変の複製により,マルチアレル性および組合せ性遺伝的多様性が生まれます.
損傷フェージングは,修復バイアス,選択,姉妹染色体交換の正確な測定を可能にします.

結論:

DNAの損傷分離は,複数の細胞世代にわたる変異パターンに影響を与える基本的なプロセスです.
このメカニズムは癌ゲノムに見られる遺伝的多様性に大きく貢献しています
損傷分離は,紫外線と化学療法剤を含む様々な変異因子の共通の特徴であり,がんの進化に広範な影響を及ぼします.

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