An integrated approach to molecular profiling supports precision diagnosis of pediatric medulloblastoma in Argentina amid the resource-constrained setting.

Medulloblastoma (MB) is the most common malignant pediatric brain tumor and shows marked molecular and clinical heterogeneity. Molecular subgrouping guides prognosis and treatment but remains scarce in low- and middle-income countries. We analyzed 84 pediatric MB cases from Argentina using a cost-effective, integrative workflow combining low- and high-complexity techniques. Tumors were classified following 2021 WHO guidelines, assessing links between molecular groups, risk, histology, location, and overall survival (OS). Non-WNT/non-SHH tumors predominated (60.7%), followed by SHH-activated (27.4%) and WNT-activated (10.7%). SHH TP53 - tumors were more common in infants, while WNT tumors occurred only in older children/adolescents. Group-specific alterations included CTNNB1 and chromosome 6 changes in WNT tumors, and MYCN and i17q in non-WNT/non-SHH tumors. SHH TP53 + tumors correlated with very high biological risk and poor OS, whereas WNT tumors had favorable outcomes. Low-cost methods resolved 90% of cases; NanoString clarified the remainder, achieving 98.8% precision. This first molecular characterization of pediatric MB in Argentina demonstrates that a tiered, conventional-tools-based approach can deliver high diagnostic accuracy and prognostic value, supporting its integration into routine care in resource-limited settings.