# Molecular Pathogenesis of Pediatric High Grade Glioma

> **NIH NIH P01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $311,897

## Abstract

Summary – Project 1 
The goals of this project are to advance understanding of the pathogenesis of pediatric high-grade glioma 
(HGG), define connections between neural development and gliomagenesis, and generate improved model 
systems with specific relevance to pediatric HGG. Pediatric HGGs comprise 15-20% of all pediatric CNS 
tumors, and remain largely incurable, with a two year survival rate of less than 30%. A subset of pediatric 
HGGs arise within the brainstem as diffuse intrinsic pontine glioma (DIPG), a tumor that arises almost 
exclusively in children with a two year survival of less than 10%. During the last funding period, we developed 
improved mouse models of HGG, and conducted in-depth genome-wide studies of pediatric HGG including 
DIPG. Results from our group and others showed distinct differences in the genetic alterations driving 
childhood and adult HGG. Most strikingly, recurrent somatic mutations in histone H3 are found in 78% of 
DIPGs and 36% of HGGs, but only rarely in young adults with glioblastoma, and not in older adult glioblastoma 
patients. Building on this progress, we propose to determine why histone H3 mutations have a unique 
selective advantage in the context of developing brain, to determine their contribution to tumorigenesis and the 
epigenomic landscape of pediatric HGG, and to develop improved model systems of pediatric HGG for 
biological studies and preclinical testing. Our studies are integrated with those in the other projects that 
explore mechanisms and genetic and epigenetic signatures driving glioma and medulloblastoma formation, 
and the identification of therapeutic targets for these devastating diseases. The project receives essential 
support from the Bioinformatics and Neuropathology Cores for the complex integrated analysis of molecular 
and histopathological features of tumors generated in model systems and comparisons with primary human 
tumors.

## Key facts

- **NIH application ID:** 10230055
- **Project number:** 3P01CA096832-15S1
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** SUZANNE J. BAKER
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $311,897
- **Award type:** 3
- **Project period:** 2002-07-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10230055

## Citation

> US National Institutes of Health, RePORTER application 10230055, Molecular Pathogenesis of Pediatric High Grade Glioma (3P01CA096832-15S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10230055. Licensed CC0.

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