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.
What are the goals of this project?
Researchers would like to validate mutations in pediatric high grade gliomas, allowing for the identification of new therapeutic targets.
What is the impact of this project?
Pediatric high grade gliomas have a great clinical need for new drug targets and this research will provide that for pHGGs with histone mutations.
Why is the CBTN request important to this project?
Researchers need samples for rare tumors with even rarer mutations, making the Children’s Brain Tumor Network’s contribution to this project invaluable.
The Children's Brain Tumor Network contributed to this project by providing H3.3G34R cell lines.
Yinnan Chen, Xu Zhang
High-grade Gliomas (HGG) or astrocytomas in children nearly always result in a dismal prognosis. Although novel therapeutic approaches are currently in development, preclinical testing has been limited, due to a lack of pediatric-specific HGG preclinical models. These models are needed to help test