Cellular and Genetic Basis of Anaplastic Medulloblastoma

间变性髓母细胞瘤的细胞和遗传基础

• 批准号: 8453423
• 负责人: Michael D. Taylor
• 金额: $ 58.12万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-04 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8453423
• 关键词: Address; Age; Aggressive behavior; Anaplasia; Anaplastic Cell; Animal Model; Behavior; Candidate Disease Gene; Cells; Cerebellum; Cerebrospinal Fluid; Child; Childhood Brain Neoplasm; Complementary DNA; DNA Transposable Elements; Data; Data Set; Disease; Epigenetic Process; Exhibits; Freezing; Gender; Gene Expression; Genes; Genetic; Genetically Engineered Mouse; Genomics; Growth; Histology; Human; Institution; Malignant - descriptor; Malignant neoplasm of brain; Mediating; Metastatic Neoplasm to the Leptomeninges; Methylation; Modeling; Molecular; Monitor; Mus; Neoplasm Metastasis; Outcome; Pathway interactions; Patients; Phenotype; Positioning Attribute; Prevention; Primary Neoplasm; Property; Research Personnel; Retroviridae; Sampling; Signaling Pathway Gene; Site; Sleeping Beauty; Subgroup; Tissues; Transplantation; base; experience; genome-wide; improved; in vivo; mRNA Expression; medulloblastoma; mouse model; neoplastic cell; neurodevelopment; outcome forecast; prevent; public health relevance; small hairpin RNA; stem cell biology; tool; tumor; tumor growth

DESCRIPTION (provided by applicant): Medulloblastoma (MB) is the most common malignant brain tumor in children. Patients whose tumors exhibit large cell/anaplastic (LCA) histology usually fail therapy and die from their disease. Improved approaches to treating these patients are likely to come from a deeper understanding of LCA tumors, including their aggressive growth properties and their invasive and metastatic behavior. Unfortunately, human LCA MB tissue is difficult to obtain, and existing genetically engineered mouse (GEM) models of MB rarely display anaplasia or metastasis. To address this problem, we have collected >100 human LCA MBs, including paired samples of primary/metastatic tumors. In addition, we have generated GEM and transplant-based models of LCA MB, and mobilized the transposable element Sleeping Beauty (SB) to promote anaplasia and metastasis in these models. Through analysis of our human and murine datasets, we propose to identify the cells and genes that drive progression in LCA medulloblastoma. This application brings together investigators from three institutions, with collective experience in neural development, stem cell biology and genomics of both human and murine MB. Our complementary backgrounds and expertise uniquely position us to investigate the cellular and molecular basis of LCA MB, and will ultimately allow us to develop more effective approaches to targeting these aggressive tumors.

描述（由申请人提供）：髓母细胞瘤（MB）是儿童中最常见的恶性脑肿瘤。肿瘤表现出大细胞/间变性（LCA）组织学的患者通常治疗失败并死于疾病。治疗这些患者的改进方法可能来自对LCA肿瘤的更深入了解，包括其侵袭性生长特性及其侵袭性和转移性行为。不幸的是，人LCA MB组织难以获得，现有的MB基因工程小鼠（GEM）模型很少显示间变性或转移。为了解决这个问题，我们收集了>100个人LCA MB，包括原发性/转移性肿瘤的配对样品。此外，我们已经产生了基于GEM和移植的LCA MB模型，并动员转座因子睡美人（SB），以促进这些模型中的间变性和转移。通过分析我们的人类和小鼠数据集，我们建议确定驱动LCA髓母细胞瘤进展的细胞和基因。该应用程序汇集了来自三个机构的研究人员，他们在神经发育，干细胞生物学和人类和小鼠MB基因组学方面具有集体经验。我们互补的背景和专业知识使我们能够研究LCA MB的细胞和分子基础，并最终使我们能够开发更有效的方法来靶向这些侵袭性肿瘤。