転移がんの統合的臨床ゲノミクス
Dan R Robinson1,2, Yi-Mi Wu1,2, Robert J Lonigro1
1Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Nature
|August 8, 2017
まとめ
この研究では500の転移性がんを 解析し TP53やCDKN2Aのような 共通遺伝子の変異を明らかにしました この発見は,転移した腫瘍とその微小環境の 総合的な分子視点を提供しています.
科学分野:
- 腫瘍学
- ゲノミクス
- 癌 生物学
背景:
- 転移は癌による死亡の主な原因です.
- 主要腫瘍と比較して,臨床的に獲得された転移性がんに関する包括的な分子データは限られている.
研究 の 目的:
- 大規模な転移性固体腫瘍の全エクソームとトランスクリプトームの配列解析を行う.
- 転移性がんの有病性および生殖系遺伝子変異を特定する.
- 転移性腫瘍の分子景観と微小環境を特徴づける
主な方法:
- 転移した固体腫瘍を持つ500人の成人の全エクソームと全トランスクリプトームのシーケンシング.
- TP53,CDKN2A,PTEN,PIK3CA,RB1を含む体内の遺伝子変異の分析
- ゲルムラインの変異,特にDNA修復経路に影響を与える変異の特定
- 遺伝子融合検出,経路活性化,免疫プロファイルのためのRNAシーケンシング
主要な成果:
- TP53,CDKN2A,PTEN,PIK3CA,およびRB1で確認された一般的な体内の変化
- 細菌系病原性変異は12. 2%の症例で発見され,75%はDNA修復欠陥に関連している.
- RNAの配列解析により 遺伝子融合,活性化経路,免疫シグネチャーが明らかになりました
結論:
- 統合的配列分析は,転移性がんの臨床的に関連する多次元的な見方を提供します.
- 分子環境と微生物環境を理解することは 転移性疾患を標的とするのに不可欠です
- この研究は様々な転移性固体腫瘍の 分子理解を広げています
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