在10,389个成年癌症中产生病原性生殖系变异
Kuan-Lin Huang1, R Jay Mashl1, Yige Wu1
1Department of Medicine, Washington University in St. Louis, Saint Louis, MO 63108, USA; McDonnell Genome Institute, Washington University in St. Louis, Saint Louis, MO 63108, USA.
Cell
|April 7, 2018
概括
这项研究在10389例患者中发现了853种癌症倾向变体,揭示了黑色素瘤和胃癌的新基因关联. 这些发现将罕见变异与功能影响联系起来,指导未来的癌症遗传测试.
科学领域:
- 遗传学
- 癌症学
- 基因组医学
背景情况:
- 生殖基因倾向变种显著增加癌症风险.
- 识别这些变异对于早期检测和个性化治疗策略至关重要.
- 之前的研究范围和规模有限.
研究的目的:
- 进行迄今为止最大规模的癌症倾向变异研究.
- 在33种癌症中发现新的基因变异关联.
- 将罕见变异与它们在瘤发育中的功能后果联系起来.
主要方法:
- 分析了33种癌症中的10389例癌症.
- 致病/可能致病变体和VUS的识别和分类.
- 综合性分析包括基因表达,异构性丧失和突变数据.
主要成果:
- 在8%的病例中发现了853种致病/可能致病变体.
- 确定了21个具有单一或跨癌症关联的基因,包括新的SDHA和PALB2链接.
- 659种瘤抑制剂和33种瘤基因变异与特定的功能后果相关.
结论:
- 这项综合性研究扩大了癌症倾向变异的范围.
- 这些发现为改进变种分类和生殖基因测试指南提供了基础.
- 综合性方法强调了罕见变异在癌症病因方面的功能影响.
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