Basic Science of Pediatric Brain Tumors

Despite decades of intensive research, pediatric brain tumors remain the most common cause of cancer-related deaths in children in North America. However, with the advent of high-throughput molecular analysis and advances in single-cell genomics, pediatric brain tumors have undergone considerable molecular and diagnostic stratifications reflective of their intertumoral and intratumoral heterogeneity. Medulloblastoma is classified into SHH, WNT, group 3, and group 4; ependymoma has been extensively characterized into subtypes which reflect both anatomic (supratentorial or posterior fossa) and molecular characteristics including those with RELA fusion; low-grade glioma has been recognized to be driven almost exclusively by RAS/MAPK signaling; high-grade glioma in children has been further characterized into anatomic and molecular subgroups in accordance with their relevant histone epigenetic drivers such as K27M and G34R mutations. Several molecularly defined entities have also been recently described, where our understanding of the heterogeneity of pediatric brain tumors is far more complex than historically described, but has opened incredible opportunities for new personalized treatment approaches. We outline and summarize the relevant characteristics of these and other important CNS neoplasms with a focus on how the basic science of these tumors is impacting clinical practice.