Molecular Heterogeneity and Cellular Diversity: Implications for Precision Treatment in Medulloblastoma

Medulloblastoma, the most common pediatric malignant brain tumor, continues to have a high rate of morbidity and mortality in childhood. Recent advances in cancer genomics, single-cell sequencing, and sophisticated tumor models have revolutionized the characterization and stratification of medulloblastoma. In this review, we discuss heterogeneity associated with four major subgroups of medulloblastoma (WNT, SHH, Group 3, and Group 4) on the molecular and cellular levels, including histological features, genetic and epigenetic alterations, proteomic landscape, cell-of-origin, tumor microenvironment, and therapeutic approaches. The intratumoral molecular heterogeneity and intertumoral cellular diversity clearly underlie the divergent biology and clinical behavior of these lesions and highlight the future role of precision treatment in this devastating brain tumor in children.