Abstract Pediatric diffuse midline gliomas (DMGs) are lethal pediatric brain tumors and are the leading cause of brain-tumor related death in children. Pediatric DMGs form in specific brain locations and developmental windows, typically in the pons and thalamus in middle childhood. Because of the locations, current treatment options are limited, and prognosis is poor. The long-term goal of our research is to understand the developmental origins of pediatric DMGs to help identify tumor growth drivers and potential therapeutic targets. Toward this goal, we have established a mouse model of H3K27M-mutant DMG using in utero electroporation (IUE) that generates spatiotemporally defined gliomas in the pons or thalamus. This strategy allows us to tailor our studies to the time frame when the tumors are forming and growing, which is not yet possible to study in humans. In the current study we are using this model to identify the molecular mechanisms involved in tumor formation and growth in the thalamus, with a particular focus on how the tumor micro-environment contributes to disease progression. This work can provide valuable insights for future preclinical studies to test efficacy of combinations of clinically relevant treatments for pediatric DMG.
Guerra et al. (Fri,) studied this question.