What are the goals of this project?
We propose to investigate germline mutations affecting histone-encoding genes in pediatric CNS tumors, and in particular diffuse midline gliomas (DMGs), from the CBTTC dataset. The majority (80%) of DMG cases harbor somatic mutations affecting histone H3-encoding genes H3F3A, HIST1H3B/C, or HIST2H3C, resulting in a lysine-27-to-methionine conversion (H3K27M). The remaining 20% of DMG cases are wildtype for somatic H3K27M mutation (H3WT), and the underlying genetic cause of H3WT DMGs remains unclear. Importantly, emerging data indicates an association between germline histone mutations and developmental/neurological disorders. Recent studies have identified de novo germline mutations in H3F3A to be associated with increased risk for developmental disorders1,2, and a case report identified H3F3A as a candidate gene associated with microcephaly, developmental delay and intellectual disability3. However, there has yet to be an extensive interrogation into the landscape of somatic and germline alterations affecting histone-encoding genes in DMG. Our objective is to interrogate germline genomes of DMG and other pediatric CNS tumors from the CBTTC dataset to profile all histone-encoding genes, and to identify novel, putative driver histone variants.
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
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. New approaches with