Biology and therapy of C11orf95-RELA fusion-driven ependymoma

摘要/摘要-总体(荷兰) 由于11号染色体上的嗜铬细胞症，大部分幕上室管膜瘤产生和 表达融合基因C11orf95-relA融合蛋白(RELAFus)。U54的目标是“生物学和治疗癌症” C11orf95-relA融合驱动的室管膜瘤是为了了解这种融合蛋白和两者的生物学 构成融合的成分，并决定这种融合的持续表达要求 蛋白质和下游的什么途径对肿瘤的发生至关重要。我们将使用一种新颖的鼠标组合 单细胞分析、免疫学、肿瘤读数的模型和人类神经干细胞系统 微环境、系统生物学和数据可视化。除了行政核心，赠款还包括 三个主要项目，一个数据可视化和共享核心。研究项目包括：项目1)机制 和C11or95和C11or95-relA融合模型(RELAFus)，项目2)治疗性的遗传询问 C11orf95-rela融合的脆弱性，以及项目3)识别具有治疗效果的小分子 RELAFUS驱动的EPN，并在EPN的临床前基因工程模型中进行测试。

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.