Diffuse intrinsic pontine glioma (DIPG) is the leading cause of death in children with brain cancers and is considered to be uniformly fatal with median overall survival of only 8-11 months. Radiation is the only therapy proven to increase survival and that by meager 3-6 months. These tumors cannot be surgically resected due to the diffuse involvement within the pons. Sequencing of DIPG genomes revealed histone mutations found in more than 80% of DIPG cases. The most common mutation occurs in the gene encoding histone 3.3 resulting in nonsynonymous change to methionine at position 27 (H3.3K27M). Smaller percentage of patients have histone 3.1 mutation variants (H3.1K27M). The histone mutations result in genome wide epigenetic changes of chromatin methylation and acetylation resulting in transcriptional dysregulation which is thought to be crucial to DIPG oncogenesis and progression. We generated epigenetic maps of the alterations induced by the aforementioned histone mutations and found profound alterations on the enhancer chromatin landscape.
What are the goals of this project?
We seek to employ WGS to identify copy number and structural alterations in the non-coding genome that may drive remodeling of enhancer chromatin in DIPG.analyze
The Children's Brain Tumor Network contributed to this project by providing access to the Pediatric Brain Tumor Atlas.
Brainstem glioma- Diffuse intrinsic pontine glioma
A presumptive diagnosis of DIPG based on classic imaging features, in the absence of a histologic diagnosis, has been routinely employed. Increasingly however, histologic confirmation is obtained for both entry into research studies and molecular characterization of the tumor.[