Nature Genet | 神经母细胞瘤起源与进化时程可用于预后判断
学术经纬约 5 分钟作者汇集了一个由100例神经母细胞瘤组成的样本库，对神经母细胞瘤队列中的突变模式进行了综合分析。研究使用高深度（约80倍）的全基因组测序数据，涵盖了100个神经母细胞瘤样本，根据国际神经母细胞瘤分期标准，覆盖了国际神经母细胞瘤分期系统确定的该疾病的所有临床阶段，其中，有67个样本来自初诊（其中7个来自转移病例），33个样本来自复发肿瘤。
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排版 | Sheila 校对 | uu
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赵强团队发现神经节苷脂风险特征可预测神经母细胞瘤预后和免疫微环境
*本文由深圳市拾玉儿童公益基金会“儿童肿瘤前沿”团队编译或约稿，文中图表均源引自文献原文。本文著作权归文章作者所有，欢迎个人转发分享，未经允许禁止转载，作者拥有所有法定权利，违者必究。如需转载，请留言或联系[email protected]。本文旨在分享儿童肿瘤科研前沿成果，不是治疗方案推荐。如需获得疾病治疗方案指导，请前往正规医院就诊。
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原文摘要（Abstract）
Neuroblastoma, the most frequent solid tumor in infants, shows very diverse outcomes from spontaneous regression to fatal disease. When these different tumors originate and how they evolve are not known. Here we quantify the somatic evolution of neuroblastoma by deep whole-genome sequencing, molecular clock analysis and population-genetic modeling in a comprehensive cohort covering all subtypes. We find that tumors across the entire clinical spectrum begin to develop via aberrant mitoses as early as the first trimester of pregnancy. Neuroblastomas with favorable prognosis expand clonally after short evolution, whereas aggressive neuroblastomas show prolonged evolution during which they acquire telomere maintenance mechanisms. The initial aneuploidization events condition subsequent evolution, with aggressive neuroblastoma exhibiting early genomic instability. We find in the discovery cohort (n = 100), and validate in an independent cohort (n = 86), that the duration of evolution is an accurate predictor of outcome. Thus, insight into neuroblastoma evolution may prospectively guide treatment decisions.
DOI: 10.1038/s41588-023-01332-y