単細胞レベルで結腸直腸がんの腫瘍内多様化
Sophie F Roerink1, Nobuo Sasaki2,3, Henry Lee-Six1
1Cancer Ageing and Somatic Mutations Programme, Wellcome Trust Sanger Insitute, Hinxton, UK.
Nature
|April 13, 2018
まとめ
大腸がん細胞は正常な細胞よりも大きく多様化し,多くの変異と独特の生物学的状態を獲得します. この腫瘍内異質性は薬剤への反応に影響し,がんを強調します.
科学分野:
- 癌 生物学
- ゲノミクス
- エピジェネティクス
背景:
- 癌は単細胞から発生しますが 異質な集団に進化します
- 腫瘍内多様性の理解は 効果的ながん治療に不可欠です
研究 の 目的:
- 結腸直腸腫瘍内の遺伝的および現象的多様性を調査する.
- 癌細胞と正常細胞の体内変異率と表遺伝子状態を比較する.
- 薬剤反応に対する腫瘍内異質性の影響を評価する.
主な方法:
- 結腸直腸がんの単細胞と隣接する正常な組織から得られたオルガノイドの特徴.
- 全ゲノム配列解析で体内の変異を特定する
- DNAメチル化とトランスクリプトーム状態の分析
- 単細胞由来オルガノイドにおける異なる薬剤反応の評価
主要な成果:
- 大腸がん細胞は,正常細胞よりもかなり多くの体内変異を伴う広範な変異多様性を示した.
- ほとんどの突然変異は 異なる突然変異プロセスによって引き起こされる 末期のクローン膨張で発生した.
- 腫瘍内におけるDNAメチル化とトランスクリプトーム状態の異質性が観察され,がんの系統形成と相関していた.
- 同じ腫瘍の密接に関連した癌細胞は,薬の感受性において顕著な違いを示した.
結論:
- 大腸がん細胞は正常細胞と比較して体内の変異率を大幅に高めています.
- 遺伝的多様化には 細胞状態の安定した遺伝的差異が伴います
- 腫瘍内異質性は薬剤反応の変動に寄与し,治療に課題をもたらす.
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