Comprehensive characterization and targeted treatment of a pediatric epithelioid glioblastoma with a rare TRIM24-NTRK2 fusion

High-grade gliomas are one of the most lethal cancers and the leading cause of cancer-related mortality in children. Standard treatment typically involves resection, chemotherapy and radiation, yet offer limited improvement in survival rates. Targeted therapies are emerging to show effect in solid tumors harboring tyrosine-kinase activating fusion genes. Here, we present a thorough characterization of an epithelioid glioblastoma in a six-year-old patient, with four relapses and a variety of different treatment strategies. We identified a rare TRIM24::NTRK2 fusion in the primary tumor, which enabled a targeted TRK-inhibitor treatment. Our findings show that the TRIM24::NTRK2 fusion initially had oncogenic abilities, but this became less imperative as the tumor evolved. A general drug resistance to TRK-inhibition was documented. This study addresses the complex and adaptive nature of pediatric epithelioid glioblastomas and highlights the need for continued molecular profiling from relapses and various tumor regions to enable multitarget treatment approaches.