腫瘍の進化における広範囲の染色体不安定性とカリオタイプ順序

Thomas B K Watkins¹, Emilia L Lim^1,2, Marina Petkovic³

¹Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, UK.

Nature

|September 4, 2020

まとめ

染色体不安定は癌の進化を促し様々な遺伝的変化を生み出しますこの研究は,これらの変化,体内複製数の変化が,しばしば並行して発生し,転移性腫瘍で濃縮されていることを示しています.

科学分野:

ゲノミクス
癌生物学
進化生物学

背景:

染色体不安定性 (CIN) は,染色体数と構造の動的変化を通してがんの進化を促す.
CINによって生成される体内複製数変異 (SCNA) は,腫瘍の適応と進行のための遺伝的多様性を提供します.

研究の目的:

様々な癌の種類におけるCINによるSCNAの異質性のパターンと結果を調査する.
全ゲノム倍増などの重要なゲノムイベントと比較して再発性SCNAイベントとそのタイミングを特定する.
転移性腫瘍における特定のSCNAの濃縮を評価する.

主な方法:

マルチサンプルのフェージングとSCNA分析は,22種類の394の腫瘍から1,421のサンプルを採取した.
1,024個の転移したサンプルを独立して分析した.
SCNAパターンの比較分析

主要な成果:

継続的なCINは,腫瘍の37%で重要な遺伝子を影響する並列の進化的イベントで,広範囲にわたるSCNAの異質性につながる.
ほとんどのSCNA損失は全ゲノム倍増 (腫瘍の49%でクローナル) に先行したが,HLAと8pの損失は倍増後でもサブクローナルに発生した.
MYCとCCND1の増幅を含む13の焦点SCNAは,転移サンプルに濃縮され,転移におけるその役割を示した.

結論:

CINは腫瘍の進化を通して並列のSCNAを誘導し,異質性に貢献します.
特定のSCNAは,腫瘍の進行と転移の間に選択され,その機能的重要性を強調します.
SCNAパターンを理解することで,標的治療や転移の可能性を予測できます.

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