对1,699例儿童白血病和固体瘤的泛癌基因组和转录组分析
Xiaotu Ma1, Yu Liu1, Yanling Liu1
1Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Nature
|March 1, 2018
概括
这项研究提供了儿童癌症的第一个泛癌基因组分析,与成人癌症相比,揭示了不同的分子异常和驱动基因. 这些发现凸显了针对儿童癌症的定制精确治疗的必要性.
科学领域:
- 基因组学
- 癌症学
- 儿童医学
背景情况:
- 全癌症分析揭示了成年癌症的分子共同点和差异.
- 儿童癌症起源于发育中的组织,缺乏全面的全癌症基因组研究.
- 现有的研究主要集中在成人上皮癌.
研究的目的:
- 在儿童白血病和固体瘤中进行体质分子异常的泛癌分析.
- 确定儿童癌症的共同和独特的基因组特征.
- 建立儿童癌症的基因组架构,以告知精确治疗的发展.
主要方法:
- 对6种基因型的1,699种儿科瘤进行全基因组,全外基因组和转录组测序.
- 用于各种基因组数据类型的统一分析框架:SNVs,indels,SVS,CNAs,基因融合,ITDs.
- 识别和分析全基因组突变特征.
主要成果:
- 在儿童癌症中发现了142个驱动基因,其中55%与成人癌症相比是独一无二的.
- 大多数 (62%) 确诊的事件是副本数量变化和结构变异.
- 发现了11个全基因组突变特征, 其中一个与形白血病的紫外线暴露有关.
结论:
- 与成人癌症相比,儿童癌症具有不同的基因组结构.
- 显著比例的突变显示可检测的等位基因转录和等位基因特异性表达.
- 这些发现强调了儿童特异性精确癌症治疗的迫切需要.
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