10136- GEN-7 ADDED CLINICAL VALUE OF WHOLE GENOME SEQUENCING FOR PEDIATRIC GLIOMA AND GLIONEURONAL TUMOR

Abstract BACKGROUND The fifth edition of the WHO Classification of Tumors of the Central Nervous System incorporates numerous genetic findings in pediatric brain tumor classification, emphasizing the significance of molecular diagnostics. In Japan, Japan Children’s Cancer Group (JCCG) Brain Tumor Committee organizes a central diagnostic system for pediatric brain tumors, including histopathology review and molecular diagnostics through a limited targeted gene analysis. However, comprehensive genome-wide analysis has not been conducted. OBJECTIVE To evaluate the clinical utility of whole genome sequencing (WGS) in pediatric glioma/glioneuronal tumor (GNT). METHODS WGS (62 cases) and RNA-seq (46 cases) were performed as part of the “ Action Plan for Whole Genome Analysis” and compared with central molecular diagnosis results (62 cases). RESULTS Central diagnostics identified 28 low-grade gliomas (44.4%), 26 high-grade gliomas (41.3%), and 8 GNTs (14.3%), with pilocytic astrocytoma accounting for 16 cases (25.8%). Adding WGS to central molecular diagnosis identified new driver mutations in 26/62 cases (41.9%). Notably, 5 additional KIAA1549::BRAF and 2 NTRK2 fusion genes were detected. In comparison with RNA-seq analysis, several cases were found in which KIAA1549::BRAF could be detected only by WGS. Additionally, PATZ1 fusion genes and several novel RAF1 fusion genes were identified. CONCLUSION WGS is useful in detecting genetic alterations that may contribute to diagnostic and therapeutic decision-making for pediatric gliomas/GNT. Incorporating WGS into the current diagnostic procedure could help develop more precise treatment strategies for pediatric glioma/GNT.