Elucidate Potential Therapeutic Targets in H3.3G34 Mutant pHGG Cells

Mutations affecting histone H3.3 proteins are now accepted as the hallmark of pediatric diffuse intrinsic pontine gliomas (DIPG) and non-brain stem pHGG. However, little is known about the mechanistic role of this histone mutation, a G34R/V mutation, in pHGG. There is an urgent and currently unmet clinical need to identify drug targets for pHGG with H3.3 G34R mutation. Researchers previously conducted genome-wide CRISPR/Cas9 screening and propose to further validate findings from this research using additional H3.3G34 mutant tumor lines. If validated, these discoveries will shed light on tumorigenesis of H3.3G34 mutant pHGG and provide potential therapeutic targets for H3.3G34 pHGG. The Children’s Brain Tumor Network will provide rare cell lines of H3.3G34 pHGG for analysis in this project.