癌を誘発する遺伝子と変異の総合的な特徴付け
Matthew H Bailey1, Collin Tokheim2, Eduard Porta-Pardo3
1Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA; McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA.
Cell
|April 7, 2018
まとめ
この研究は26のツールを用いて 9,423の腫瘍にわたる癌の誘発遺伝子と変異を 総合的に分類しています 299の誘導遺伝子と 3,400以上の変異を明らかにし 精密な腫瘍学を発展させました
科学分野:
- ゲノミクス
- コンピュータ生物学
- 腫瘍学
背景:
- 精密腫瘍学の進歩には 分子がんの誘発因子の特定が不可欠です
- ドライバー識別のための既存のアルゴリズムは数多くありますが,大きなデータセットで組み合わせたり最適化したりすることはめったにありません.
研究 の 目的:
- 癌を誘発する遺伝子と変異をカタログ化するために,包括的なPanCancerとPanSoftwareの分析を行う.
- ドライバーの識別のための複数の計算ツールを体系的に組み合わせ,最適化します.
主な方法:
- 癌ゲノムアトラス (TCGA) の 33 件のプロジェクトから 9,423 件の腫瘍エクソムの分析.
- ドライバー遺伝子と突然変異のカタログに 26の異なる計算ツールを使用した.
- 変異の特徴と実験的検証のために,配列と構造に基づく分析を使用した.
主要な成果:
- 解剖学的な部位と癌/細胞タイプに影響を及ぼす299のドライバー遺伝子を特定した.
- 3千4百以上の 誤った遺伝子変異を 発見した
- 実験的な検証により,予測された突然変異の60%から85%が確率的な要因であると確認された.
- マイクロサテライト不安定 (MSI) 腫瘍と高いPD-1/PD-L1発現との関連性が見つかりました.
- 分析された腫瘍の57%が 臨床的に対処可能な出来事を 抱えていることが判明した.
結論:
- この研究は 癌の遺伝子と変異の 最も広範な発見を表しています
- この発見は将来のがん研究と臨床応用のための 基礎的なリソースと青写真を提供します.
- 駆動因子と対応可能な変異の包括的なカタログは 精密腫瘍学の努力を加速させるでしょう
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