フィンランドの癌家族におけるPALB2の再発性突然変異
Hannele Erkko1, Bing Xia, Jenni Nikkilä
1Department of Clinical Genetics, University of Oulu and Oulu University Hospital, FIN-90029 OYS, Finland.
Nature
|February 9, 2007
まとめ
PALB2遺伝子の変異であるc.1592delTは,遺伝性乳がんと関連しています. この変異はDNA修復とBRCA2結合を阻害し,PALB2が乳がんの感受性遺伝子であることを示唆しています.
科学分野:
- 遺伝学 遺伝学とは
- 腫瘍学 腫瘍学
- 分子生物学は分子生物学である.
背景:
- 遺伝性乳がんはしばしばBRCA1,BRCA2,および他の遺伝子と関連付けられていますが,これらは症例の半分未満を説明します.
- BRCA2相互作用タンパク質PALB2は,DNA損傷反応と腫瘍抑制に不可欠である.
- 新種の感受性遺伝子の発見は,遺伝性がんリスクを理解するために極めて重要です.
研究 の 目的:
- 遺伝性乳がんにおけるPALB2変異の役割を調査する.
- 特定されたPALB2フレームシフト変異 (c.1592delT) が乳がんリスクの増加と関連しているかどうかを判断する.
- 家族性前立腺がんに対するPALB2変異の潜在的貢献を調査する.
主な方法:
- ファミリアルの乳がん症例におけるPALB2変異のスクリーニングとフィンランドにおける集団コントロール.
- c.1592delT変異から生じる切断されたPALB2タンパク質の機能分析.
- 未選択の乳がん患者とその家族におけるc.1592delT変異のさらなるスクリーニング.
主要な成果:
- PALB2のフレームシフト変異c.1592delTは,対照群と比較して,家族性乳がん症例において,著しく高い頻度で発見されました.
- 断片化されたPALB2タンパク質は,BRCA2結合能力の低下と同類の再結合およびクロスリンク修復の欠陥を示した.
- c.1592delT変異は,未選択の乳がん患者,主に家族歴のある患者で約4倍濃縮された.
- 前立腺がんを患った複数の世代の1つの家族も,c.1592delTアレルを分離しました.
結論:
- PALB2は乳がんの感受性遺伝子として特定されています.
- PALB2のc.1592delT変異は,遺伝性乳がんと関連しています.
- 変異したPALB2は,家族性前立腺がんの発生にも役割を果たす可能性があります.
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