Microglial Mosaicism in BRAFV600E Glioma Development

Pediatric Low Grade Gliomas (pLGG) are the most common brain tumor in children and BRAFV600E is a mutation found in up to 20% of pLGG cases. This mutation is associated with a poor prognosis. In the majority of cases, factors leading to progression and malignant transformation are unknown. There is growing evidence of the existence of somatic (cells that are not reproductive cells) mutations in human non-tumoral tissues, including driver mutations associated with cancers, that can affect cellular fitness and lead to the development of inflammatory diseases. Researchers have conducted previous studies in mice that strongly suggests that the presence of mosaic somatic mutations in the tumor microenvironment, in this case microglia, contributes to tumor grade or aggressiveness. Therefore, researchers would like to expand this novel hypothesis in human pediatric samples. Early detection of mosaic mutations, genetically distinct populations of cells within one individual, in the tumor microenvironment could inform risk of progression, guide the design of therapeutic interventions and ultimately improve pediatric glioma patient outcomes. Results from this research could reveal complementary somatic mosaicism as a driver not only in pediatric glioma, but possibly in other developmental tumors, which is a novel concept that has not been explored. This important work is supported through the provision of rare tumor tissue and blood samples by the Children’s Brain Tumor Network.