在芬兰的癌症家族中,PALB2中出现了反复发生的突变
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
概括
一个PALB2基因突变,c.1592delT,与遗传性乳腺癌有关. 这种突变损害了DNA修复和BRCA2结合,这表明PALB2是乳腺癌易感基因.
科学领域:
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 遗传性乳腺癌通常与BRCA1,BRCA2和其他基因有关,但这些解释不到一半的病例.
- 与BRCA2相互作用的蛋白PALB2对于DNA损伤反应和瘤抑制至关重要.
- 发现新的易感基因对于了解遗传性癌症风险至关重要.
研究的目的:
- 研究PALB2突变在遗传性乳腺癌中的作用.
- 为了确定确定的PALB2框架转移突变 (c.1592delT) 是否与乳腺癌风险增加有关.
- 探索PALB2突变对家族性前列腺癌的潜在贡献.
主要方法:
- 在芬兰的家族乳腺癌病例和人口对照中查PALB2突变.
- 来自c.1592delT突变的截断PALB2蛋白的功能分析.
- 在未经选择的乳腺癌患者及其家属中进一步查c.1592delT突变.
主要成果:
- 与对照组相比,在家族性乳腺癌病例中,PALB2框架转移突变c.1592delT的频率显著更高.
- 截断的PALB2蛋白显示BRCA2结合能力降低,同类重组和交叉连接修复缺陷.
- 在未经选择的乳腺癌患者中,c.1592delT突变大约是四倍的丰富,主要是那些有家族病史的患者.
- 一个患有前列腺癌的多代家庭也分离了c.1592delT等位基因.
结论:
- PALB2被确定为乳腺癌易感基因.
- 在PALB2中c.1592delT突变与遗传性乳腺癌有关.
- 突变PALB2也可能在家族性前列腺癌的发展中发挥作用.
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