Abstract Background Central nervous system (CNS) tumors are the most common pediatric solid tumors and a major cause of childhood cancer-related mortality. With the advent of molecular profiling, the World Health Organization (WHO) has increasingly incorporated genomic data into its diagnostic framework. However, clinical grade comprehensive genomic profiling data from large cohorts of unselected pediatric CNS patients remain limited. Methods We summarize genomic data from clinically validated DNA/RNA profiling of 574 CNS tumors from 532 pediatric patients at a single institution and assess the clinical utility of these findings. Results Tier 1/2 variants were identified in 94.1% of patients with 90.8% of patients yielding clinically impactful findings. These findings resulted in a diagnosis change in 4.2% of patients and refined the histologic diagnosis in 22%. Prognostically relevant alterations were identified in 10% of patients while potential therapeutic targets were identified in 38%. Additionally, serial tumor testing in 36 patients enabled assessment of tumor evolution and differentiation of recurrent/relapsed tumors from independent primary tumors. Furthermore, 23.9% of patients were suspected to have germline pathogenic/likely pathogenic variants, with 73.2% confirmed through germline testing, representing 11.3% of the cohort. Conclusions Our study provides a large, integrated clinical dataset of genomic alterations in pediatric CNS tumors. Our findings highlight the clinical significance of genomic profiling of pediatric CNS tumors and underscore the necessity of integrating genomic results with pathologic, radiologic, and clinical features to ensure accurate tumor diagnosis and facilitate personalized, risk-adapted patient management.
Wong et al. (Fri,) studied this question.