Patient-derived tumoroids recapitulate the morphologic and molecular features of pediatric brain tumors.

Pediatric brain tumors (PBTs) are the leading cause of cancer-related mortality in children. Despite advances in next-generation sequencing (NGS) deepening our understanding of the molecular features of PBT, the lack of preclinical models that capture their complexity and diversity remains a significant barrier to developing less toxic and more effective treatments. We have established 20 ex-vivo patient-derived tumoroid (PDTs) cultures from fresh surgical material of a wide range of PBTs, including low- and high-grade gliomas, medulloblastomas, and even rarer tumor entities such as a CNS tumor with BCOR alteration. Immunofluorescence, NGS analysis, and DNA methylation profiling revealed that the PDTs faithfully mirrored the cellular nature, the genetic and epigenetic landscape of their matched primary tumors. Our study shows the feasibility of generating PDTs, even from rarer entities, that recapitulate the genetic and epigenetic features of primary tumors, highlighting their potential as models for tumor biology studies and precision medicine.