代替的転写イニシアチブは,がんにおける新しいALKイソフォームの発現につながる
Thomas Wiesner1,2, William Lee3,4, Anna C Obenauf5
1Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York 10065, USA.
Nature
|October 8, 2015
まとめ
新しいアナプラスティックリンパ腫キナーゼ (ALK) 異形,ALK ((ATI) は,遺伝的変化ではなく,代替転写開始によるメラノーマの11%で活性化されます. この発見は 癌の治療に 新たな治療目標をもたらします
科学分野:
- 腫瘍学
- 分子生物学
- 遺伝学
背景:
- 遺伝的異常を超えた腫瘍遺伝子の活性化のメカニズムはよく理解されていません.
- アナプラスティックリンパ腫キナーゼ (ALK) は既知の腫瘍遺伝子ですが,その活性化経路は完全に解明されていません.
研究 の 目的:
- 癌における腫瘍遺伝子の活性化の新しいメカニズムを特定し,特徴づけること.
- メラノーマや他の癌における新発見のALKイソフォームの役割を調査する.
主な方法:
- 新しいALK同型を特定するためのトランスクリプトミックの分析.
- 活性転写マーク (H3K4me3,RNAポリメラーゼII) を評価するためのクロマチンの免疫流出.
- マウスにおける細胞増殖試験と体内の腫瘍形成モデル.
主要な成果:
- 新しいALK同型 (ALK(ATI) が,イントロン19の代替転写開始部位から発現した.
- ALK ((ATI)) は,約11%のメラノーマで, sporadically 他の癌で発見されましたが,正常な組織ではありません.
- ALKの発現はALKの位置における遺伝的異常とは無関係であり,腫瘍発生信号伝達,細胞増殖,腫瘍発生を促した.
結論:
- 癌における腫瘍遺伝子の活性化のための新しいメカニズムを表しています.
- ALKの活性がALK阻害剤によって抑制される可能性があるため,ALK (AT) は潜在的な治療標的である.
- ALK ((ATI)) を発現する腫瘍を有する患者に有益である.
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