Pediatric brain tumors are the leading cause of cancer related death in childhood. Distinct from their adult brain tumor counterparts, they harbor a relative paucity of somatic driver alterations. Moreover, the tumor micro-environment of pediatric brain tumors is modulated by normal brain development, and the tumors exhibit distinct growth characteristics at different ages. Low-grade gliomas are defined by single driver alterations that activate the MAPK and mTOR signaling pathways. In contrast, high-grade gliomas harbor histone mutations, in addition to additional events that perturb the TP53 axis and activate growth factor signaling and MYC pathways. These tumors exhibit relentless growth after diagnosis, and do not have any curative options.
This presentation will review our work to characterize the genetic and transcriptional landscape of pediatric glioma to understand the evolutionary pressures that shape the formation of gliomas, and their subsequent response to therapies.