エクストラクロモソーム腫瘍遺伝子の増幅は腫瘍の進化と遺伝的異質性を誘発する
Kristen M Turner1, Viraj Deshpande2, Doruk Beyter2
1Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, California 92093, USA.
Nature
|February 9, 2017
まとめ
エクストラ染色体DNA (ecDNA) は,正常な細胞とは異なり,ヒトがんのほぼ半分に含まれています. この円形のDNAは腫瘍遺伝子を増幅し 癌の進化を加速し 腫瘍内異質性を増加させます
科学分野:
- ゲノミクス
- 癌 生物学
- 分子遺伝学
背景:
- 人間の細胞は23組の染色体を持っています.
- ガンにおける遺伝子増幅は染色体または染色体外DNA (ecDNA) で発生する.
- 癌におけるecDNAの有病率と機能的意義は,ほとんど不明である.
研究 の 目的:
- 人間の癌におけるecDNAの頻度と機能的重要性を調査する.
- 偏見のないecDNA検出と分析の方法を開発する.
- 癌の進化におけるecDNAの役割を理解するために
主な方法:
- 17種類のがん細胞の2572個の全ゲノム配列と細胞遺伝分析
- 染色体と染色体外DNAの構造モデリング
- 統合されたecDNA分析のためのECdetectソフトウェアパッケージの開発.
主要な成果:
- ヒトのがんのほぼ50%でecDNAが検出され,腫瘍の種類によって頻度が異なっていた.
- ecDNAは正常な細胞ではめったに見られませんでした.
- ドライバ・オンコゲンはしばしばecDNAで増幅され,トランスクリプトレベルが上昇した.
- 数学的モデリングと定量分析により,ecDNA増幅は染色体増幅よりも効果的に腫瘍遺伝子の複製数と腫瘍内異質性を高めることが確認された.
結論:
- 腫瘍遺伝子の増幅に大きく寄与している.
- 癌の進化を加速し,腫瘍内異質性を高める上で重要な役割を果たしています.
- この発見は,がん治療の潜在的な標的として,ecDNAを強調しています.
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