肺アデノカルシノーマにおけるがんゲノムの特徴づけ
Barbara A Weir1, Michele S Woo, Gad Getz
1Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Nature
|November 6, 2007
まとめ
この研究では,371件の肺腺がんのコピー数の変化を分析し,57件の再発的なイベントを特定しました. 研究者らは,NKX2-1を肺がんを誘発する新型原発がん遺伝子候補として発見した.
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:
- ソマティックDNAの変異は,ヒトの癌に不可欠です.
- ゲノム全体の解析の進歩は,がんのゲノム特徴付けを推進しています.
- 肺腺がんは,標的治療のための包括的なゲノムプロファイリングを必要とします.
研究 の 目的:
- 主要肺アデノカルシノーマのコピー数変化を体系的に特徴づけるために.
- 肺アデノカルシノーマ発症に関与する新規候補遺伝子を特定する.
- 肺がんにおけるゲノムイベントの状況を理解する.
主な方法:
- 371件の肺原発性アデノカルシノーマ腫瘍の分析.
- ゲノム全体の分析のために,密度の高い単一ヌクレオチドポリモルフィズム (SNP) 配列を使用した.
- 候補遺伝子を特定するためにゲノムと機能分析を行いました.
主要な成果:
- 57の有意に繰り返されるコピー番号変更イベントを特定しました.
- 39の自体染色体腕のうち26は,一貫した大規模複製数変化を示した.
- 24の増幅と7のホモジゴス欠損を含む31の再発的焦点イベントを発見した.
- ~12%のサンプルでNKX2-1増幅 (14q13.3) を新型原発がん遺伝子候補として特定しました.
結論:
- 肺腺がんを誘発する多くの遺伝子は未発見のままである.
- NKX2-1は,肺腺がんに関与する新型候補原発がん遺伝子である.
- コピー数の変化は,肺がんにおける潜在的な治療標的の重要な源である.
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