转移性癌症的综合性临床基因组学
Dan R Robinson1,2, Yi-Mi Wu1,2, Robert J Lonigro1
1Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Nature
|August 8, 2017
概括
这项研究对500种转移性癌症进行了测序, 揭示了TP53和CDKN2A等常见基因变异. 这些发现为转移性瘤及其微观环境提供了全面的分子视图.
科学领域:
- 癌症学
- 基因组学
- 癌症生物学
背景情况:
- 转移是癌症死亡的主要原因.
- 与原发性瘤相比,对于临床获得的转移性癌症存在有限的综合分子数据.
研究的目的:
- 在大量转移性实体瘤上进行全外体和转录组测序.
- 在转移性癌症中识别流行体内和生殖系遗传变异.
- 描述转移性瘤的分子格局和微环境.
主要方法:
- 在500名患有转移性实体瘤的成年患者中进行全外和全转录组测序.
- 对体基因变异的分析,包括TP53,CDKN2A,PTEN,PIK3CA和RB1.
- 鉴定生殖系变异,特别是影响DNA修复途径的变异.
- 用于基因融合检测,通路激活和免疫分析的RNA测序.
主要成果:
- 在TP53,CDKN2A,PTEN,PIK3CA和RB1中发现的流行体质变化.
- 在12.2%的病例中发现了生殖系致病变体,75%与DNA修复缺陷有关.
- 通过RNA测序发现了基因融合,激活途径和免疫特征.
结论:
- 综合序列分析为转移性癌症提供了临床相关的多维视图.
- 了解分子格局和微环境对于向转移性疾病至关重要.
- 这项研究扩大了对多种转移性实体瘤的分子理解.
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