The oncogenic fusion landscape in pediatric CNS neoplasms

Pediatric neoplasms in the central nervous system (CNS) are the leading cause of cancer-related deaths in children. Recent developments in molecular analyses have greatly contributed to a more accurate diagnosis and risk stratification of CNS tumors. Additionally, sequencing studies have identified various, often entity specific, tumor-driving events. In contrast to adult tumors, which often harbor multiple mutated oncogenic drivers, the number of mutated genes in pediatric cancers is much lower and many tumors can have a single oncogenic driver. Moreover, in children, much more than in adults, fusion proteins play an important role in driving tumorigenesis, and many different fusions have been identified as potential driver events in pediatric CNS neoplasms. However, a comprehensive overview of all the different reported oncogenic fusion proteins in pediatric CNS neoplasms is still lacking. A better understanding of the fusion proteins detected in these tumors and of the molecular mechanisms how these proteins drive tumorigenesis, could improve diagnosis and further benefit translational research into targeted therapies necessary to treat these distinct entities. In this review, we discuss the different oncogenic fusions reported in pediatric CNS neoplasms and their structure to create an overview of the variety of oncogenic fusion proteins to date, the tumor entities they occur in and their proposed mode of action. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00401-022-02405-8.