メラノーマの主なサブタイプの全ゲノム風景
Nicholas K Hayward1,2, James S Wilmott1,3, Nicola Waddell2,4
1Melanoma Institute Australia, The University of Sydney, North Sydney, Sydney, New South Wales 2065, Australia.
Nature
|May 4, 2017
まとめ
全ゲノム配列解析により,皮膚がんのUV放射線や, 粘膜や膜のメラノーマの未知の要因など, メラノーマの様々な原因が明らかになりました. 非コードDNA変異は メラノーマ発症に重要な役割を果たします
科学分野:
- ゲノミクス
- 腫瘍学
- 皮膚科
背景:
- メラノーマのサブタイプ (皮膚性,アクラル性,粘膜性) は,全般的に異なる発症率を示しています.
- 様々なメラノーマサブタイプの 遺伝的基盤を理解することは 標的型療法にとって 極めて重要です
研究 の 目的:
- 皮膚,アクラ,粘膜のメラノーマの全ゲノム配列を分析する
- メラノーマのサブタイプにおける 新種の変異シグネチャーと 影響を受けた遺伝子を特定する
- メラノーマの病原性における非コード変異の役割を調べる
主な方法:
- メラノーマのサブタイプの全ゲノム配列解析
- 暗号化と非暗号化変異の分析
- 変異シグネチャーと有意に変異した遺伝子の特定
主要な成果:
- 皮膚メラノーマは紫外線による変異を示し,アクラルおよび粘膜メラノーマは構造的変化と未知の変異シグネチャーを示します.
- 非コード変異とコード変異は,同じ数の遺伝子に影響します.
- 重要な変異遺伝子は,BRAF,CDKN2A,NRAS,TP53,NF1,SF3B1が含まれています. TERTプロモーター変異が最も頻繁です.
- ほとんどのメラノーマはMAPKやPI3Kのような信号伝達経路に 作用する変異がある
結論:
- メラノマは様々な発がん性プロセスから生じます 太陽光にさらされることとは無関係です
- 非コーディングゲノムは メラノーマ発症に大きく関わっています
- ゲノム解析により,サブタイプ特有の変異の風景と潜在的な治療目標が明らかになる.
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