ヒトメラノーマにおける非常に頻繁なTERTプロモーター変異
Franklin W Huang1, Eran Hodis, Mary Jue Xu
1Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Science (New York, N.Y.)
|January 26, 2013
まとめ
テロメラーゼ逆転写酵素 (TERT) プロモーターの2つの新しい突然変異は,メラノーマの71%で特定され,遺伝子の活動を増加させました. これらの発見は,遺伝子調節領域の突然変異が,がんの発症における重要なメカニズムであることを示唆しています.
科学分野:
- 腫瘍学 腫瘍学
- 遺伝学 遺伝学とは
- 分子生物学は分子生物学である.
背景:
- ヒトがんゲノムの体系的な配列解析は,主にタンパク質をコードする遺伝子の変異を特定し,遺伝子の調節領域にはあまり焦点を当てていない.
- テロメラーゼ逆転写酵素 (TERT) 遺伝子はテロメアの維持に不可欠であり,癌に関与しています.
- 制御領域の変異を理解することは,新しいがんのメカニズムを明らかにする鍵です.
研究 の 目的:
- 人間のがんにおけるTERT遺伝子プロモーターの変異を特定し,特徴づけること.
- これらの突然変異がTERT遺伝子転写に与える機能的影響を調査する.
- これらの突然変異が様々な癌のタイプに及ぶ頻度を決定する.
主な方法:
- メラノーマのサンプル全ゲノム配列解析.
- レポーターアッセイは,TERTプロモーター活動に対する突然変異の影響を評価するアッセイである.
- 特定された変異の検出のために,多様な癌細胞系をスクリーニングする.
主要な成果:
- TERT遺伝子のコアプロモーターに2つの異なる変異が特定され,分析されたメラノーマの71%で発生しました.
- これらの変異は,E-twenty-six (ETS) 転写因子のための新しい結合部位を作り出します.
- レポーターアッセイでは,変異したTERTプロモーターによる転写活動の2〜4倍の増加が示されました.
- 同じ変異は,様々ながん細胞系の16%で発見され,膀および肝細胞がんでは顕著な頻度がありました.
結論:
- TERTプロモーターのソマティック変異は,メラノーマやその他の癌で頻繁に見られる現象です.
- これらの変異はTERT遺伝子転写を強化し,腫瘍発生に潜在的に寄与する.
- 遺伝子調節領域の変異は,がん発症における重要な,かつては過小評価されていたメカニズムを表しています.
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