Modeling H3 G34R and BCOR-Altered Glioma Pathogenesis Using Neural Stem Cells
Background:
H3 G34R and BCOR ITD alterations are genetic events recently found in a subset of pediatric “high-grade gliomas” – aggressive brain tumors for which no cures currently exist. These genes are thought to regulate many signaling pathways through "epigenetic" modification of the overall DNA structure. However, we do not currently understand in detail how they make brain cells into tumors, and few models which can be used to the testing of therapies models exist.
Project Goal:
We propose generating new models of these tumors which can be used to improve our understanding of how the mutations drive cancer formation in the brain, and which also may be helpful for the development and testing of new treatments. To do so, we will introduce the H3 G34R or BCOR ITD mutations into murine or human brain cells. With these models, we can see how those alterations affect other signaling pathways, as well as the modification of DNA by methylation. We hope to share these new insights and models with other researchers around the world to improve the diagnosis and treatment of children with deadly brain tumors.
