MITFにおける新しい再発性突然変異は,家族性および散発性メラノーマの発生を誘発する
Satoru Yokoyama1, Susan L Woods, Glen M Boyle
1Department of Dermatology, Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Massachusetts 02114, USA.
Nature
|November 15, 2011
まとめ
研究者らは,家族性メラノーマリスクに関連した新しい遺伝子変異体,マイクロフタルミア関連転写因子 (MITF) E318Kを特定しました. この発見は,全ゲノム配列を解析することを強調しています.
科学分野:
- 遺伝学 遺伝学とは
- 腫瘍学 腫瘍学
- 皮膚科 皮膚科について
背景:
- ファミリアルメラノーマリスクは,CDKN2AとCDK4のみが主要な予備性遺伝子として特定され,完全に理解されていません.
- これらの既知の遺伝子は,メラノーマファミリーにおける遺伝的傾向のマイノリティを占めています.
研究 の 目的:
- 全ゲノム配列解析を用いて,家族性メラノーマの感受性に関連した新しい遺伝子を特定する.
- メラノーマの予備性におけるマイクロフタルミア関連転写因子 (MITF) 遺伝子の役割を調査する.
主な方法:
- メラノーマファミリーの個体の全ゲノム配列解析. メラノーマファミリーの個体の全ゲノム配列解析.
- 新しいMITF変種 (E318K) を携えた家族における結合分析.
- オーストラリアとイギリスの人口におけるケース・コントロール関連研究.
- MITF E318Kの変種に関する機能分析.
主要な成果:
- MITF (E318K) の新しい生殖系変種は,メラノーマに罹患しやすい家族で特定されました.
- MITF E318K変種は,大規模な症例対照群でメラノーマと有意な関連性を示した.
- この変種は,メラノーマのリスク増加,家族歴,多発性一次性メラノーマ,ナエブス数の増加,非青い目の増加と関連していました.
- 機能的研究では,MITF E318K変異によって,スモイル化の障害と標的遺伝子調節の変化が明らかになりました.
結論:
- MITFは新型メラノーマ誘発性遺伝子として特定されています.
- E318K変種は,メラノーマの中間リスク因子です.
- 全体ゲノムシーケンシングは,疾患の感受性に関連した希少変異を発見するための貴重なツールです.
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