Primary malignant brain tumors remain a disproportionate cause of morbidity and mortality in humans. A number of studies exploring the
cancer genome of
brain tumors across ages using integrated genetics and epigenetics and next-generation sequencing technologies have recently emerged. This has led to considerable advances in the understanding of the basic biology and pathogenesis of
brain tumors, including the most malignant and common variants in children:
gliomas and
medulloblastoma. Notably, studies of pediatric
brain tumors have identified unexpected oncogenic pathways implicated in
tumorigenesis. These range from a single pathway/molecule defect such as abnormalities of the
mitogen-activated protein kinase pathway, considered to be a hallmark of
pilocytic astrocytomas, to alterations in the epigenome as a critical component altered in many subgroups of high-grade
brain tumors. Importantly, the type, timing, and spatial clustering of these molecular alterations provide a better understanding of the pathogenesis of the respective
brain tumor they target and critical markers for
therapy that will help refine pathological grading. We summarize these novel findings in pediatric
brain tumors, which also are put in the context of the evolving notion of molecular pathology, now a mandated tool for proper classification and
therapy assignment in the clinical setting.