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局所性前立腺がんの進化は 臨床的攻撃性を高めています
Shadrielle Melijah G Espiritu1, Lydia Y Liu1, Yulia Rubanova2
1Informatics and Biocomputing Program, Ontario Institute for Cancer Research, Toronto, ON M5G 1L7, Canada.
Cell
|April 24, 2018
まとめ
前立腺がんの進化は 異なる腫瘍のサブタイプを明らかにします 多数のサブクローンを持つ多細胞性腫瘍は再発率が高く,活発な監視のための新しいバイオマーカーを示唆しています.
科学分野:
- 腫瘍学
- 遺伝学
- 癌 生物学
背景:
- ほとんどの前立腺がんは 成長が遅いのですが 転移して致死する人もいます
- 腫瘍の進化を理解することは 臨床結果の予測に不可欠です
研究 の 目的:
- 局所性前立腺がんの腫瘍を 復元するために
- サブクローンアーキテクチャと臨床的結果を相関させ,重要な遺伝的イベントを特定する.
主な方法:
- 293の局所性前立腺腫瘍の遺伝子組み換え
- 臨床結果データ,サブクローン構造,および変異シグネチャーの分析.
- 腫瘍の進化過程で変異した遺伝子の特定
主要な成果:
- 59%の患者は複数の腫瘍サブクローンがあり,有害な特徴が関連していました.
- 腫瘍の進化は,点変異/消去から増幅および変異シグネチャーへと進行する.
- 特定の遺伝子 (MTOR,NKX3-1,RB1) が選択的に変異した.
- 低リスクのモノクローナル腫瘍は低発症率 (7%),高リスクのポリクローナル腫瘍は高発症率 (61%) であった.
結論:
- サブクローン構造は前立腺がんの再発の 重要な予測因子です
- ポリクローン腫瘍は再発のリスクが高いことを示します.
- 進化に敏感なバイオマーカーは 低リスクの前立腺がんの 積極的な監視戦略を改善する可能性があります
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