Pediatric high-grade gliomas (pHGGs) is a deadly disease that requires robust research to develop effective therapies. Recently, recurring mutations in genes encoding histone H3 have been identified in pHGGs, including H3K27M and H3G34R/V. Histones are the proteins that pack DNA together and influences caused by such mutations outside of DNA are considered epigenetic changes. Pediatric HGGs with these mutations show distinct gene expression patterns and epigenetic landscapes, suggesting that the mechanisms of tumor growth might be different and they might require different therapeutic strategies. Pediatric HGGs with H3G34R/V, which is less well-studied than pHGGs with H3K27M, will be the major focus of this study. The goals of this project are to identify direct genomic targets of H3G34R/V in pHGG cell lines. This study could reveal previously unknown tumorigenesis mechanisms and novel drug targets of H3G34R/V pHGGs. Cell lines derived from different H3G34R/V pHGG patients have different genetic backgrounds, therefore findings in one specific cell line may not apply to others. To find mechanisms and drug targets that apply to most patients with H3G34R/V, it is critical to perform experiments in multiple H3G34R/V pHGG cell lines and identify the common mechanisms and potential therapeutic targets. This is why the Children’s Brain Tumor Network’s contribution of preclinical models to this project is so important.
What are the goals of this project?
The main goal of this project is to identify direct genomic targets of H3G34R/V in pHGG cell lines.
What is the impact of this project?
Once targets are identified, further work can be done to develop personalized therapeutics for patients with pediatric high grade gliomas with HG34r/V mutations.
Why is the CBTN request important to this project?
Researchers need access to multiple samples of this rare tumor type, samples only available through the Children’s Brain Tumor Network.
The Children's Brain Tumor Network is contributing to this project by providing preclinical models.
Yang Shi, PhD
Yang Shi joined Harvard Medical School as an assistant professor in 1991 and was appointed a Professor of Pathology in 2004. He is currently a Professor of Cell Biology. He is also the Merton Bernfield Professor of Neonatology in the Division of Newborn Medicine at Children’s Hospital Boston. Yang
Harvard Medical School
Chen Zhou, BS
I am interested in the mechanisms of gene expression regulation in response to environmental changes, especially those mediated by epigenetic modifications.
Boston Children's Hospital
Jamie Anastas, PhD
Dr. Anastas is studying how mutations in chromatin-associated factors affect heterochromatin organization in pediatric cancer.
Boston Children's Hospital
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