MDB-25. LARGE CELL/ANAPLASTIC MEDULLOBLASTOMA REPRESENTS MORE THAN ONE DISEASE ENTITY

Abstract Medulloblastoma (MB) with predominant large cell or anaplastic cytological features have been identified to be associated an aggressive clinical course and poor survival. Because cases can show mixed cytologies, these histologically defined MB types were merged in the recent WHO classification of tumors CNS cell/anaplastic (LC/A) MB. In this study, we collected FFPE samples 137 LC/A all age groups (0-39 years) diagnosed at DGNN Brain Tumor Reference Center Bonn, Germany, performed a comprehensive histological, immunophenotypical, genetic epigenetic analysis by next-generation panel sequencing (NGS), 450k/850k methylation bead-array hybridization molecular inversion probe (MIP) technology. 73% showed histology, 27% histology. Methylation-based subtyping that cohort represented different biological entities: 6% WNT-MB, 7% SHH-MB-TP53-wildtype, 10% SHH-MB-TP53-mutant, 77% non-WNT/non-SHH (with subtype II). High-resolution copy number profiling MIP demonstrated MYC amplification 40% was highly infant disease On contrary, histology non-infant disease, MYCN SHH activation. By NGS detected recurrent mutations 37 MB-related genes; frequency individual genes differed significantly between genetically types. Our data clearly demonstrate represent entities. Therefore, also respect future development targeted treatment approaches malignant types, they should precisely as separate