増殖制御における深層組織特異性は,がんの誘導因子とアヌプロイドのパターンの根底にある
Laura Magill Sack1, Teresa Davoli1, Mamie Z Li1
1Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Cell
|March 27, 2018
まとめ
科学者は癌細胞の増殖を制御する遺伝子を特定し 殆どの遺伝子は組織特異であることが判明しました これらの増殖要因は 腫瘍の複製数の変化と関連しており 癌の遺伝学と 血管新生性に関する洞察を明らかにしています
科学分野:
- ゲノミクス
- 癌 生物学
- 分子遺伝学
背景:
- 癌は制御不能な細胞増殖によって特徴づけられる.
- 特に遺伝子配分で作用する 腫瘍発生要因を特定することは 依然として課題です
- ゲノミクスは 癌のゲノム構造を詳細に説明していますが 機能的なドライバーの識別には 精細化が必要です
研究 の 目的:
- 癌細胞の増殖を制御する遺伝子を特定する
- 増殖レギュレータと腫瘍における体内複製数変化 (SCNA) の関係を調査する.
- SCNAと癌の誘発因子の選択に 基づく遺伝子ネットワークの構造を理解する.
主な方法:
- 人間の開いた読書フレーム (ORF) のモジュール化されたバーコードライブラリの構築.
- ORFライブラリの高通量スクリーニングで,複数の細胞タイプの増殖レギュレータを特定します.
- 関連する腫瘍からのSCNAデータにおける遺伝子濃縮の分析.
- In vivoスクリーニングで検査結果を検証する.
主要な成果:
- 遺伝子の約10%が増殖レギュレータとして特定された.
- 確認されたほとんどの増殖調節剤は高組織特異性を示した.
- 増殖の原動力は,同種の腫瘍内のSCNAの有意な濃縮を示した.
- SCNAに関連したドライバは,腫瘍におけるアヌプロイドパターンを予測するのに役立ちました.
- 147の増幅された遺伝子と107の削除された遺伝子は,潜在的SCNA関連ドライバとして特定されました.
結論:
- 組織特異的な遺伝ネットワークはSCNAと様々な癌の誘発因子の選択に影響を与えます
- SCNAは,特定の拡散要因に,文脈に依存した方法で結びついています.
- この研究は,SCNAに関連した癌の誘発因子のカタログを大幅に拡張し,腫瘍アヌプロイド構造の洞察を提供します.
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