Background and Objectives:Central Nervous System (CNS) pediatric tumors represent the most common solid tumors in children with a wide variability in terms of survival and therapeutic response. By contrast to their adult counterpart, the mutational landscape of pediatric CNS tumors is characterized by oncogenic fusions rather than multiple mutated genes. CNS pediatric tumors associated with oncogenic fusions represent a complex landscape of tumors with wide radiological, morphological and clinical heterogeneity. In the fifth CNS WHO classification, there are few pediatric CNS tumors for which diagnosis is based on a single oncogenic fusion. This work aims to provide an overview of the impact of rare oncogenic fusions (NTRK,ROS,ALK,MET,FGFR,RAF,MN1,BCORandCICgenes) on pathogenesis, histological phenotype, diagnostics and theranostics in pediatric CNS tumors. We report four cases of pediatric CNS tumors associated withNTRK(n= 2),ROS(n= 1) andFGFR3(n= 1) oncogenic fusion genes as a proof of concept.Cases presentation and literature review:The literature review and the cohort that we described here underline that most of these rare oncogenic fusions are not specific to a single morpho-molecular entity. Even within tumors harboring the same oncogenic fusions, a wide range of morphological, molecular and epigenetic entities can be observed.Conclusions: These findings highlight the need for caution when applying the fifth CNS WHO classification, as the vast majority of these fusions are not yet incorporated in the diagnosis, including grade evaluation and DNA methylation classification.
背景与目的：中枢神经系统（CNS）儿童肿瘤是儿童中最常见的实体肿瘤，其生存率和治疗反应存在显著差异。与成人中枢神经系统肿瘤相比，儿童中枢神经系统肿瘤的突变特征主要表现为致癌性融合基因，而非多基因突变。携带致癌性融合基因的儿童中枢神经系统肿瘤构成了一类复杂的肿瘤群体，在影像学、形态学和临床特征上表现出高度异质性。在第五版中枢神经系统世界卫生组织（WHO）分类中，仅有少数儿童中枢神经系统肿瘤的诊断基于单一致癌性融合基因。本研究旨在综述罕见致癌性融合基因（涉及NTRK、ROS、ALK、MET、FGFR、RAF、MN1、BCOR及CIC基因）对儿童中枢神经系统肿瘤的发病机制、组织学表型、诊断及诊疗策略的影响。我们通过报告四例携带致癌性融合基因（NTRK基因融合2例、ROS基因融合1例、FGFR3基因融合1例）的儿童中枢神经系统肿瘤病例，以验证相关概念。 病例展示与文献综述：文献综述及本文描述的病例队列表明，大多数罕见致癌性融合基因并不局限于单一形态-分子实体。即使在携带相同致癌性融合基因的肿瘤中，也可观察到广泛的形态学、分子学及表观遗传学差异。 结论：这些发现提示在应用第五版中枢神经系统WHO分类时需保持谨慎，因为绝大多数此类融合基因尚未被纳入诊断体系，包括分级评估和DNA甲基化分类。
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