Biology and therapy of C11orf95-RELA fusion-driven ependymoma

C11orf95-RELA 融合驱动的室管膜瘤的生物学和治疗

• 批准号: 10394666
• 负责人: ERIC C. HOLLAND
• 金额: $ 4.12万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10394666
• 关键词: Biology; Cell Nucleus; Chimeric Proteins; Chromosome 11; Core Grant; Ependymoma; Event; Fusion Protein Expression; Gene Fusion; Genetic; Genetic Engineering; Goals; Human; Immunology; Modeling; Oncogenes; Oncogenic; Pathway interactions; Phase; RELA gene; Research Project Grants; Supratentorial; System; Systems Biology; Testing; Therapeutic; Therapeutic Effect; chromothripsis; data sharing; data visualization; mouse model; novel; parent grant; pre-clinical; single cell analysis; small molecule; stem cells; tumor; tumor microenvironment; tumorigenesis

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.

摘要/总结-总体（荷兰） 由于11号染色体上的染色体断裂事件，大多数幕上室管膜瘤产生和 表达基因融合体C11 orf 95-RELA融合体（RELAFus）。U 54的目标是“生物学和治疗”， C11 orf 95-RELA融合驱动的室管膜瘤是为了了解这种融合蛋白的生物学特性和两者 组成融合体并决定该融合体持续表达的要求的成分 蛋白质和下游途径对肿瘤发生至关重要。我们将使用一种新颖的鼠标组合 模型和人类神经干细胞系统与单细胞分析，免疫学，肿瘤 微环境、系统生物学和数据可视化。除了行政核心外，该赠款还 三个主要项目，一个是数据可视化和共享核心。研究项目包括：项目1）机制 和C11 or 95和C11 or 95-RELA融合模型（RELAFus），项目2）治疗性免疫缺陷的遗传询问 C11 orf 95-RELA融合的脆弱性，以及项目3）鉴定在癌症中具有治疗作用的小分子。 RELAFus驱动的EPN和测试他们在临床前基因工程模型的EPN。