Pediatric High-Grade Gliomas and DIPG

Recent genomic studies of pediatric high-grade gliomas (pHGGs) have unraveled important new clues into the pathogenesis of these tumors. One novel insight that was previously unappreciated is the role of epigenetic alterations in pediatric gliomagenesis. This was realized when mutations in histone 3.3/3.1 (H3.3/H3.1) were identified in these tumors. A related concept is that certain genetic alterations only occur in a region-specific manner within the central nervous system. As an example, K27M H3.3/H3.1 mutations are present in high-grade gliomas that arise along the midline of the central nervous system while G34R and G34V H3.3 mutations are present in high-grade gliomas that arise in the cerebral cortex. In addition, the realization that gliomas that harbor histone mutations are mutually exclusive of isocitrate dehydrogenase (IDH) mutant gliomas, which primarily arise in adults, has reinforced the notion that pediatric gliomas and adult gliomas are biologically disparate diseases. Incorporating this new data within the framework of our existing knowledge of the genetic alterations of pHGGs gives new hope that we will successfully identify effective therapies for these tumors in the upcoming decade.