Ependymoma is the third most common brain tumor of childhood, and can occur anywhere in the nervous system. Although classically described as a single entity, it is now very clear that different compartments of ependymoma are totally different diseases, specifically the supratentorial, posterior fossa and spinal compartments. Current therapies are comprised of surgery and radiation, in children as young as one, and result in survival rates of 30-70% depending on the extent of surgery and the molecular biology of the tumor, with survivors having significant neurocognitive sequelae.
Supratentorial ependymoma has been shown to harbor recurrent fusions on chromosome 11, which lead to a fusion protein of C11orf95 and RelA, a coactivator of NFkB in 70% of patients, and less commonly fusions of YAP1 and MAML2. A methylation based classifier has shown that supratentorial ependymoma comprises 3 distinct subgroups, specifically ST-EPN-RELA, ST-EPN-YAP1 and ST-EPN-SE (subependymoma), with ST-EPN-RELA having a very poor prognosis, and ST-EPN-YAP1 are infants with a very good prognosis. However, the vast majority of supratentorial ependymoma are ST-EPN-RELA, and within ST-EPN-RELA there is a wide range of clinical heterogeneity. Currently, it is unclear which patients are predicted to do well within this group, specifically whether there exists biological heterogeneity that can help guide clinical care.
What are the goals of this project?
The goals of this project are to determine the frequency of non-RELA/YAP1 supratentorial ependymoma through genome wide methylation profiling, elucidate the frequency of non-cannonical fusions across supratentorial ependymoma and compare the gene expression and methylation patterns of non-RELA fused and RELA-fused
What is the impact of this project?
This study will allow us to determine the full genomic spectrum of supratentorial ependymoma, and characterize non-canonical fusions which can help prioritize approaches in clinical trials.
Why the CBTN request is important to this project?
Considering the rarity of supratentorial ependymoma and the overall difficulties in obtaining the current discovery cohort, using CBTN specimens provides an opportunity to validate both the non-canonical fusion incidence in a sufficiently large cohort with frozen tissue amenable to both RNA sequencing and DNA methylation. The available of tissue from institutions treating with standard protocols will also allow for clinical interpretation of these non-canonical fusions.
The Children's Brain Tumor Network contributed to this project by providing tumor DNA, tumor RNA and access to the Pediatric Brain Tumor Atlas.
Vijay Ramaswamy, MD, PhD, FRCPC
My overall research focus is the translational genomics of medulloblastoma and ependymoma with a focus on recurrent disease. My previous and ongoing work has been primarily to apply clinical correlates to recent genomic findings, with an overarching goal of identifying new and more robust risk st
Ependymomas arise from ependymal cells that line the ventricles and passageways in the brain and the center of the spinal cord. Ependymal cells produce cerebrospinal fluid (CSF). These tumors are classified as supratentorial or infratentorial. In children, most ependymomas are infratentorial tumo