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致命的な転移性前立腺がんの進化史
Gunes Gundem1, Peter Van Loo1,2,3, Barbara Kremeyer1
1Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
Nature
|April 2, 2015
まとめ
転移は,たった一つの癌細胞ではなく,複数の癌細胞のクローンを通して広がる可能性があります. この研究は,複雑な転移パターンを明らかにし,前立腺がんの治療抵抗性を報告しています.
科学分野:
- 腫瘍学 腫瘍学
- 癌生物学 癌生物学について
- 進化医学とは,進化医学である.
背景:
- 癌の進化には,ダーウィンの選択が関与し,腫瘍サブクローンへと導きます.
- 転移の形成は癌による死亡の90%の原因ですが,転移の原理は十分に理解されていません.
- ポリクローナルシード (複数のクローン) とクローン間の協力は,マウスモデルによって示唆されています.
研究 の 目的:
- ヒトのがんにおけるポリクローナルシディングの決定的な証拠を提供すること.
- 前立腺がんにおける転移の間のクローン関係を調査する.
- メタスタシの拡散と,アンドロゲン欠乏療法に対する耐性を理解する.
主な方法:
- 10人の前立腺がん患者の原発性腫瘍と多発性転移の全ゲノム配列解析.
- 転移性拡散パターンをマッピングするために,サブクローナルアーキテクチャの統合分析.
- 腫瘍抑制遺伝子とアンドロゲン受容体のシグナル伝達経路遺伝子における遺伝的変異の特徴.
主要な成果:
- メタスタシスからメタスタシスへの拡散は一般的であり,モノクローナルシードと複数のクローンのポリクローナル移転の両方を含む.
- 5件の症例では,複数の腫瘍クローンが転移部位間で転移している証拠が示されました.
- 腫瘍抑制遺伝子の病変は通常単一のイベントとして発生しますが,アンドロゲン受容体の経路変異は転移の間の収束進化を示します.
結論:
- ヒトの悪性腫瘍は,単細胞起源の仮説に異議を唱えて,ポリクローナルシードを示しています.
- 複合的な転移パターンが解明され,転移間拡散も含まれています.
- この発見は,前立腺がんの進行およびアンドロゲン欠乏療法に対する耐性についての理解を深める.
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