結腸がんにおける再発性R-スポンディン融合

Somasekar Seshagiri¹, Eric W Stawiski, Steffen Durinck

¹Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA. sekar@gene.com

Nature

|August 17, 2012

まとめ

研究者らは,Wnt経路とクロマチンの改造遺伝子を含む結腸がん遺伝子の新しい再発性突然変異を特定しました. これらの発見は,結腸がん治療の新たな治療標的を提示する可能性がある.

科学分野:

ゲノミクスゲノミクスとは
がん生物学がん生物学
分子腫瘍学分子腫瘍学

背景:

がんにおけるゲノム変異を理解することは,標的治療の開発に不可欠です.
大腸がんは,腫瘍の進行を促す複雑な遺伝子変化を示します.

研究の目的:

主要なヒト大腸腫瘍のコホートにおけるエクソーム,トランスクリプトーム,コピー番号の変異を体系的に分析する.
潜在的治療標的となる大腸がんにおける新たな再発性突然変異と遺伝子融合を特定する.

主な方法:

次世代シーケンシング (NGS) は,70組以上のヒト大腸腫瘍を分析するために適用されました.
総合的な分析には,エクソームシーケンシング,トランスクリプトームシーケンシング (RNA-seq),コピー番号変異プロファイリングが含まれていました.

主要な成果:

TCF7L2,TET2,TET3,ERBB3.3における新たな再発性突然変異を含む36,303のタンパク質変異を特定した.
ATM. を含む,著しく変異した23の癌遺伝子候補を発見した. IGF2の増幅と過剰発現が確認されました.
腫瘍の10%でRSPO2とRSPO3を含む再発性遺伝子融合が発見され,Wntシグナル伝達を強化し,APC変異と相互排斥しています.

結論:

この研究では,Wnt経路とクロマチン再構成遺伝子変異,RSPO遺伝子融合を含む,結腸がんにおける新しい遺伝子変異を特定しました.
これらの発見は,結腸癌の腫瘍発生に関する新しい洞察を提供し,介入のための潜在的な新しい治療標的を強調します.

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