Molecular Mechanisms of TRAF7 Mutant Aggressive Meningiomas

TRAF7突变侵袭性脑膜瘤的分子机制

基本信息

批准号：
9887847
负责人：
MURAT GUNEL
金额：
$ 56.86万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9887847
关键词：
Acute Adult Anaplastic Meningioma Animal Model Architecture Automobile Driving Benign Benign Meningiomas Biochemical Biological Assay Blood - brain barrier anatomy Brain Brain Neoplasms Cell Line Cell Proliferation Cells ChIP-seq Clinical Trials Code Collection DNA Methylation Drug Targeting Effectiveness Event Excess Mortality Future Genes Genital system Genomic approach Genomics Glioblastoma Glioma Hand Histologic Histology Human Incidence Intracranial Neoplasms Intraneural perineurioma Invaded Malignant - descriptor Meningeal Mesothelioma Molecular Morbidity - disease rate Mutate Mutation Neurologic Neurologic Deficit Oncogenic Operative Surgical Procedures Pathway interactions Patients Pharmaceutical Preparations Population Primary Brain Neoplasms Principal Investigator Public Health Radiation Recurrence Reporting Research Resected Role Signal Pathway Signaling Molecule Stroke Structure Subgroup Testing Therapeutic United States Untranslated RNA adenoma base driver mutation drug candidate drug efficacy efficacy testing epigenomics exome exome sequencing genomic profiles inhibitor/antagonist insight meningioma mouse model mutant neurovascular new therapeutic target next generation sequencing novel therapeutics programs protein function response skull base subcutaneous transcriptome sequencing tumor ubiquitin isopeptidase ubiquitin ligase ubiquitin-protein ligase whole genome

Acute Adult Anaplastic Meningioma Animal Model Architecture Automobile Driving Benign Benign Meningiomas Biochemical Biological Assay Blood - brain barrier anatomy Brain Brain Neoplasms Cell Line Cell Proliferation Cells ChIP-seq Clinical Trials Code Collection DNA Methylation Drug Targeting Effectiveness Event Excess Mortality Future Genes Genital system Genomic approach Genomics Glioblastoma Glioma Hand Histologic Histology Human Incidence Intracranial Neoplasms Intraneural perineurioma Invaded Malignant - descriptor Meningeal Mesothelioma Molecular Morbidity - disease rate Mutate Mutation Neurologic Neurologic Deficit Oncogenic Operative Surgical Procedures Pathway interactions Patients Pharmaceutical Preparations Population Primary Brain Neoplasms Principal Investigator Public Health Radiation Recurrence Reporting Research Resected Role Signal Pathway Signaling Molecule Stroke Structure Subgroup Testing Therapeutic United States Untranslated RNA adenoma base driver mutation drug candidate drug efficacy efficacy testing epigenomics exome exome sequencing genomic profiles inhibitor/antagonist insight meningioma mouse model mutant neurovascular new therapeutic target next generation sequencing novel therapeutics programs protein function response skull base subcutaneous transcriptome sequencing tumor ubiquitin isopeptidase ubiquitin ligase ubiquitin-protein ligase whole genome

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项目摘要

PROJECT SUMMARY / ABSTRACT Meningiomas are the most common primary brain tumors. While typically of benign histology, they can be associated with significant neurological morbidity and have the potential for malignant transformation. In our previous studies, we completed genomic analysis of over 700 meningiomas using whole exome and targeted next-generation sequencing, identifying driver mutations in 12 genes and establishing mutually exclusive molecular subgroups. We now propose to investigate the molecular mechanisms underlying the formation of TRAF7-dependent meningiomas (which represent up to one quarter of all meningiomas), undertake molecular genomic analyses to identify somatic coding and non-coding or genomic events in TRAF7 tumors that progress to higher grades. We also propose to test and validate candidate drug efficacy using primary cultures from surgically resected meningiomas carrying TRAF7 aberrations, as well as mouse models of meningioma that we have established.

项目摘要 /摘要脑膜瘤是最常见的原发性脑肿瘤。虽然通常是良性组织学的与明显的神经系统发病率相关，并具有恶性转化的潜力。在我们的先前的研究，我们使用整个外显子组完成了700多个脑膜瘤的基因组分析，并针对下一代测序，识别12个基因中的驱动器突变并建立相互排斥分子亚组。现在，我们建议研究形成的分子机制 TRAF7依赖性脑膜瘤（代表所有脑膜瘤的四分之一），承担分子基因组分析以鉴定TRAF7肿瘤中的体细胞编码和非编码或基因组事件这是更高成绩的进展。我们还建议使用原发性测试和验证候选药物疗效来自手术切除的脑膜瘤的培养物，携带TRAF7畸变，以及小鼠模型我们已经建立的脑膜瘤。