在儿童癌症中发生的基因组变异
Susanne N Gröbner1,2,3, Barbara C Worst1,2,3,4, Joachim Weischenfeldt5,6
1Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
Nature
|March 1, 2018
概括
这项研究分析了24种类型的961种儿童瘤的基因变异. 研究结果显示,与成年人相比,儿童癌症的遗传特征不同,近50%的癌症可用于未来的临床试验.
科学领域:
- 癌症学
- 遗传学
- 癌症生物学
背景情况:
- 全癌症分析通过检查不同癌症类型的共同点和差异,为癌症生物学提供了新的见解.
- 了解儿童癌症的遗传变化对于开发向疗法至关重要.
研究的目的:
- 在儿童,青少年和年轻成年人瘤的大型瘤群中对基因变异进行全面分析.
- 与成人癌症相比,确定突变频率和显著突变基因的差异.
- 探索儿童瘤中可能发生的药物事件.
主要方法:
- 标准化工作流程用于分析来自24种不同分子类型的961种瘤.
- 基因变异的识别和分类,包括突变频率,显著突变的基因和结构/副本数变异.
- 基因变异,生殖系变异,TP53突变状态和突变特征之间的相关性分析.
主要成果:
- 与成人癌症相比,在儿童癌症中观察到突变频率和显著突变基因的明显差异.
- 149个潜在的癌症驱动基因的遗传变化将瘤分为小突变和结构/副本数变异类.
- 与TP53突变状态和突变特征相关的是结构变异,超平分体和染色体.
- 在7-8%的儿科瘤中,有诱导性生殖系变异.
- 几乎50%的儿科新生体有潜在的可用药事件.
结论:
- 与成人癌症相比,儿童癌症具有不同的遗传特征.
- 显著比例的儿童瘤是治疗干预的可操作目标.
- 这些发现对未来儿科瘤学临床试验的设计具有高度意义.
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