The majority of diffuse midline glioma (DMG) cases harbor mutations affecting histone H3-encoding genes. Histones are the proteins that pack DNA together, allowing them to have epigenetic (or non-gene) influences on tumors. The remaining 20% of DMG cases are H3WT DMGs, and the underlying genetic cause of H3WT DMGs remains unclear. Emerging data indicates an association between histone mutations that are passed down and developmental/neurological disorders and recent studies have begun to identify such mutations. However, there has yet to be extensive research into the landscape of genetic alterations affecting histone-encoding genes in DMG. Researchers propose to investigate germline mutations affecting histone-encoding genes in pediatric central nervous system tumors, and in particular diffuse midline gliomas (DMGs), from data provided by the Children’s Brain Tumor Network. The objective of this project is to analyze the inheritable (germline) genomes of DMG and other pediatric CNS tumors in the hopes of improving diagnostics, prognostics, and therapeutic options. This work is made possible through access to comprehensive data in the Pediatric Brain Tumor Atlas.
What are the goals of this project?
Researchers will investigate mutations affecting histone-encoding genes in pediatric central nervous system tumors, and in particular diffuse midline gliomas (DMGs), in the pursuit of identifying new driver histone variants to improve overall outcome for patients.
What is the impact of this project?
A deeper understanding of DMG types and their genetic drivers will in turn lead to advancements in the understanding the development and care of such tumors.
Why is the CBTN request important to this project?
This work would not be possible without the provision of high quality tumor data through access to the Pediatric Brain Tumor Atlas.
Javad Nazarian, PhD, MSc
I am an investigator at the Center for Genetic Medicine in Children’s National Hospital in Washington, D.C., and an assistant professor in Integrative Systems Biology at the George Washington University. I received my PhD from the George Washington University in Genetics in 2005. My dissertation res
Children’s National Hospital
Sebastian Waszak, PhD
My lab focuses on precision medicine for children, adolescents, and young adults with cancer; in particular children with brain tumours. We combine approaches from population genomics, cancer genomics, and systems genetics to understand the genetic basis of cancer, the somatic evolution of cancer ce
University of Oslo
Children’s National HospitalJoined on
Each year, the Brain Tumor Institute at Children’s National evaluates more than 100 new patients with brain tumors, and is recognized as a world leader in childhood brain tumor care and research. Children’s National has pioneered novel pediatric brain tumor therapies, including new molecularly-targe
University of Oslo
Center for Molecular Medicine Norway (NCMM)
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. New approaches with