A systematic look at a childhood tumor Neuroblastomas—the most common tumor type in infants—develop from fetal nerve cells, and their clinical course is highly variable. Some neuroblastomas are fatal despite treatment, whereas others respond well to treatment and some undergo spontaneous regression without treatment. Ackermann et al. sequenced more than 400 pretreatment neuroblastomas and identified molecular features that characterize the three distinct clinical outcomes. Low-risk tumors lack telomere maintenance mechanisms, intermediate-risk tumors harbor telomere maintenance mechanisms, and high-risk tumors harbor telomere maintenance mechanisms in combination with RAS and/or p53 pathway mutations. Science, this issue p. 1165 Neuroblastomas that are positive for telomere maintenance mechanisms are associated with a poorer prognosis. Neuroblastoma is a pediatric tumor of the sympathetic nervous system. Its clinical course ranges from spontaneous tumor regression to fatal progression. To investigate the molecular features of the divergent tumor subtypes, we performed genome sequencing on 416 pretreatment neuroblastomas and assessed telomere maintenance mechanisms in 208 of these tumors. We found that patients whose tumors lacked telomere maintenance mechanisms had an excellent prognosis, whereas the prognosis of patients whose tumors harbored telomere maintenance mechanisms was substantially worse. Survival rates were lowest for neuroblastoma patients whose tumors harbored telomere maintenance mechanisms in combination with RAS and/or p53 pathway mutations. Spontaneous tumor regression occurred both in the presence and absence of these mutations in patients with telomere maintenance–negative tumors. On the basis of these data, we propose a mechanistic classification of neuroblastoma that may benefit the clinical management of patients.

中文翻译：

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神经母细胞瘤临床表型的机制分类

对儿童肿瘤的系统观察神经母细胞瘤——婴儿中最常见的肿瘤类型——由胎儿神经细胞发育而来，其临床病程变化很大。尽管接受治疗，一些神经母细胞瘤仍是致命的，而其他神经母细胞瘤对治疗反应良好，有些未经治疗就会自然消退。阿克曼等人。对 400 多个预处理神经母细胞瘤进行了测序，并确定了表征三种不同临床结果的分子特征。低危肿瘤缺乏端粒维持机制，中危肿瘤具有端粒维持机制，高危肿瘤具有端粒维持机制与 RAS 和/或 p53 通路突变相结合。科学，这个问题 p。1165 端粒维持机制阳性的神经母细胞瘤预后较差。神经母细胞瘤是交感神经系统的小儿肿瘤。其临床过程从自发性肿瘤消退到致命进展。为了研究不同肿瘤亚型的分子特征，我们对 416 个预处理神经母细胞瘤进行了基因组测序，并评估了其中 208 个肿瘤的端粒维持机制。我们发现肿瘤缺乏端粒维持机制的患者预后良好，而具有端粒维持机制的肿瘤患者的预后要差得多。其肿瘤具有端粒维持机制以及 RAS 和/或 p53 通路突变的神经母细胞瘤患者的存活率最低。在端粒维持阴性肿瘤患者中，无论存在和不存在这些突变，都会发生自发性肿瘤消退。在这些数据的基础上，我们提出了一种可能有益于患者临床管理的神经母细胞瘤的机械分类。