Molecular Mechanisms of TRAF7 Mutant Aggressive Meningiomas

TRAF7突变侵袭性脑膜瘤的分子机制

• 批准号: 10400940
• 负责人: MURAT GUNEL
• 金额: $ 50.86万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 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/10400940
• 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; Genitalia; 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; Neurofibromin 2; 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; 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

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