儿童癌症倾向和进化约束:从1,127名患有癌症的儿童的生殖基因组中获得的新课程
Ulrik Kristoffer Stoltze1, Thomas van Overeem Hansen2, Jon Foss-Skiftesvik3
1Rigshospitalet, Copenhagen East, Denmark.
概括
基因组分析显示,患有癌症的儿童的癌症倾向综合征 (CPSs) 病原体变异率高于预期. 这凸显了胚胎基因组测试对于早期诊断和个性化儿科瘤治疗的重要性.
科学领域:
- 基因组学就是基因组学.
- 儿科瘤学 儿科瘤学
- 进化生物学 进化生物学
背景情况:
- 癌症倾向综合征 (CPSs) 是儿童癌症的主要原因,并影响治疗策略.
- 以前的儿科癌症研究尚未充分利用基因组进化指标来预测疾病透率或识别新的CPS.
研究的目的:
- 研究基因组进化指标在预测癌症倾向综合征透率方面的实用性.
- 用一种以进化为导向的方法识别新的癌症倾向综合征.
主要方法:
- 生殖线全基因组测序 (WGS) 在18岁之前被诊断患有癌症的儿童的前队列上进行.
- 以进化为指导的负担分析将受约束基因中的私有生殖系变异与大型参考外体数据集 (gnomAD) 相比较.
主要成果:
- 1,127名参与者中有16%携带CPS基因的致病变体;651名儿童中有9%携带致病变体,这一比例明显高于之前报告的.
- 与参考成年人相比,受约束基因中观察到过多的功能丧失 (LoF) 变异,表明负达尔文选择性压力.
- 在进化上对损伤最不耐受的基因中发现了pLoF变异的显著残留丰富,超过了预期.
结论:
- 在CPS基因中LoF变异的高患病率强调了儿童癌症患者常规生殖系基因组分析的必要性.
- 将基因组数据与临床表型联系起来,对于推进儿科瘤护理和实现诊断前干预至关重要.
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