Ahmed Melek, Sieben Anne, Van Genechten Toon, Libbrecht Sasha, Gilis Nathalie, De Praeter Mania, Fricx Christophe, Calò Pierluigi, Van Campenhout Claude, D'Haene Nicky, Witte Olivier De, Kempen Léon C Van, Lammens Martin, Salmon Isabelle, Lebrun Laetitia
Division of Pathology, Antwerp University Hospital (UZA), 2650 Edegem, Belgium.
Instituut Born Bunge (IBB), 2610 Wilrijk, Belgium.
Cancers (Basel). 2024 Sep 30;16(19):3344. doi: 10.3390/cancers16193344.
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 (, , , , , , , and genes) on pathogenesis, histological phenotype, diagnostics and theranostics in pediatric CNS tumors. We report four cases of pediatric CNS tumors associated with ( = 2), ( = 1) and ( = 1) oncogenic fusion genes as a proof of concept. 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. : 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.
中枢神经系统（CNS）儿科肿瘤是儿童中最常见的实体瘤，其生存率和治疗反应差异很大。与成人中枢神经系统肿瘤不同，儿科中枢神经系统肿瘤的突变格局以致癌性融合而非多个突变基因特征。与致癌性融合相关的儿科中枢神经系统肿瘤代表了一个复杂的肿瘤格局，具有广泛的放射学、形态学和临床异质性。在第五版世界卫生组织（WHO）中枢神经系统肿瘤分类中，很少有儿科中枢神经系统肿瘤的诊断基于单一的致癌性融合。这项工作旨在概述罕见致癌性融合（、、、、、、、和基因）对儿科中枢神经系统肿瘤发病机制、组织学表型、诊断及诊疗的影响。我们报告了4例与（=2）、（=1）和（=1）致癌性融合基因相关的儿科中枢神经系统肿瘤病例，作为概念验证。我们在此进行的文献综述和病例队列强调，这些罕见致癌性融合中的大多数并非特定于单一的形态分子实体。即使在携带相同致癌性融合的肿瘤中，也可观察到广泛的形态学、分子和表观遗传学实体。：这些发现凸显了在应用第五版WHO中枢神经系统肿瘤分类时需谨慎，因为这些融合中的绝大多数尚未纳入诊断，包括分级评估和DNA甲基化分类。
