Biology and therapy of C11orf95-RELA fusion-driven ependymoma

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ABSTRACT/SUMMARY – OVERALL (HOLLAND) Due to a chromothripsis event on chromosome 11, the majority of supratentorial ependymomas generate and express the gene fusion C11orf95-RELA fusion (RELAFus). The goal of the U54 titled “Biology and therapy of C11orf95-RELA fusion-driven ependymoma is to understand the biology of this fusion protein and the two components that make up the fusion and determine the requirements for continued expression of this fusion protein and what pathways downstream are critical for oncogenesis. We will use a combination of novel mouse models and human neuro stem cell systems with readouts of single cell analysis, immunology, tumor microenvironment, systems biology, and data visualization. In addition to the administrative core, the grant has three main Projects, a data visualization and sharing core. The research projects include, Project 1) Mechanisms and models of C11or95 and C11or95-RELA fusions (RELAFus), Project 2) Genetic interrogation of therapeutic vulnerabilities for C11orf95-RELA fusion, and Project 3) Identifying small molecules with therapeutic effects in RELAFus -driven EPN and testing them in preclinical genetically engineered models of EPN.