Landscape of Germline Histone Mutations in Pediatric Brain Tumor Patients

The majority of diffuse midline glioma (DMG) cases harbor mutations affecting histone H3-encoding genes. Histones are the proteins that pack DNA together, allowing them to have epigenetic (or non-gene) influences on tumors. The remaining 20% of DMG cases are H3WT DMGs, and the underlying genetic cause of H3WT DMGs remains unclear. Emerging data indicates an association between histone mutations that are passed down and developmental/neurological disorders and recent studies have begun to identify such mutations. However, there has yet to be extensive research into the landscape of genetic alterations affecting histone-encoding genes in DMG. Researchers propose to investigate germline mutations affecting histone-encoding genes in pediatric central nervous system tumors, and in particular diffuse midline gliomas (DMGs), from data provided by the Children’s Brain Tumor Network. The objective of this project is to analyze the inheritable (germline) genomes of DMG and other pediatric CNS tumors in the hopes of improving diagnostics, prognostics, and therapeutic options. This work is made possible through access to comprehensive data in the Pediatric Brain Tumor Atlas.