遺伝的および転写的進化は,がん細胞ラインの薬剤反応を変化させる
Uri Ben-David1, Benjamin Siranosian1, Gavin Ha1,2
1Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Nature
|August 10, 2018
まとめ
ヒトの癌細胞系は 培養における進化により 重要な遺伝的多様性を表しています この異質性は薬剤への反応に影響し,がん研究における注意深い特徴化の必要性を強調しています.
科学分野:
- ゲノミクス
- 癌 生物学
- 細胞の異質性
背景:
- ヒトの癌細胞系は 重要な研究ツールです
- 細胞系統の進化とその影響は完全に理解されていません.
- 細胞系における遺伝的および転写的異質性については,さらなる研究が必要である.
研究 の 目的:
- ヒトの癌細胞系における遺伝的および転写的異質性の範囲と起源を調査する.
- 薬剤反応を含む細胞系進化の機能的結果を理解する.
- 研究の再現性を向上させるため,細胞系変異を測定するための枠組みを提供すること.
主な方法:
- 2つの研究室でヒトがん細胞系106のゲノム解析
- 乳がん細胞系MCF7の27種のゲノム解析
- 細胞の進化を研究するためのバーコード実験と単細胞のクローン分析.
- 321の抗癌化合物に対するMCF7菌株の薬剤反応試験
主要な成果:
- MCF7を含むヒトの癌細胞系において,広範なクローン多様性と急速な遺伝的多様性が観察された.
- 遺伝子変化は遺伝子発現,細胞形態,増殖の変化と相関する.
- 細胞系進化は,培養条件に敏感な陽性クローン選択によって引き起こされる.
- 抗癌薬の反応の有意な差異は,細胞系株間で発見され,最大75%の化合物が異なる有効性を示した.
結論:
- ヒトの癌細胞系は,培養における進化的プロセスにより,著しい遺伝的多様性と異質性を示す.
- この異質性は,機能的な結果,特に薬物反応に大きな影響を及ぼします.
- 研究者は再現可能で信頼性の高いがん研究を確実にするために 細胞系変異を把握し 測定する必要があります
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