Imaging regional gene expression variability in brain tumor associated seizures

脑肿瘤相关癫痫发作的区域基因表达变异成像

• 批准号: 8873267
• 负责人: Jong Woo Lee
• 金额: $ 8.86万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8873267
• 关键词: Adult Glioma; Adverse effects; Affect; Antiepileptic Agents; Area; Benchmarking; Brain; Brain Neoplasms; Brain region; Characteristics; Data; Data Analyses; Data Set; Diagnosis; Epilepsy; Foundations; Gene Expression; Genes; Genomics; Glioma; Glutamate Transporter; Glutamates; Goals; Image; Individual; Lead; Life Expectancy; Linear Models; Link; Location; Magnetic Resonance Imaging; Maps; Methods; Modality; Molecular; Morbidity - disease rate; National Institute of Neurological Disorders and Stroke; Nature; Neoplasms; Outcome; Pathway interactions; Patients; Play; Quality of life; Research; Seizures; System; Temporal Lobe; The Cancer Genome Atlas; Tumor-Associated Process; Validation; Work; cancer imaging; cost; design; differential expression; experience; extracellular; frontal lobe; image archival system; imaging modality; improved; neuroimaging; novel; overexpression; programs; public health relevance; repository; targeted treatment; tool; treatment strategy; tumor

 DESCRIPTION (provided by applicant): Tumor associated seizures (TAS) are present in approximately half of the patients with brain tumors and cause a marked decrease in the quality of life in these patients. Understanding the underlying mechanisms of TAS, crucial in developing new therapies, is hindered by its multifactorial nature, as both imaging and genomic characteristics play key roles. Examining the contribution of neuroimaging and gene expression in TAS in concert will more readily lead to discovery of biologically relevant mechanisms of TAS than by assessment of either modality in isolation. The central hypothesis of this study is that tumor gene expression is associated with TAS in a brain region-specific manner. This study will utilize the genomic and MRI data from carefully curated public repositories: The Cancer Genome Atlas (TCGA), Repository for Molecular BRAin Neoplasia DaTa (REMBRANDT, for validation), and The Cancer Imaging Archive (TCIA). The specific aims are: 1) Using TCGA dataset, identify genes and gene sets that are differentially expressed in patients with versus without TAS. 2) Using TCGA and TCIA datasets, characterize brain regions where gene expression has significant correlation with TAS. Particular focus will be on the expression of SLC7A11 which encodes the system xc- glutamate transporter, which causes a well-established mechanism of TAS through dysregulation of glutamate. The datasets will be assessed for differential expression of other novel genes and gene sets. Newly developed gene expression statistical image mapping tools will be utilized to analyze in what brain region the expression of SLC7A11 and other key genes are significantly associated with TAS, with the hypothesis that SLC7A11 expression have a higher correlation with TAS in the temporal, as compared to the frontal, lobes. Genes that are correlated to TAS because of association with tumor location, but without specific epileptogenic mechanisms, will demonstrate no regions of significance. Incorporating both gene expression and imaging information simultaneously is a novel and powerful method of characterizing TAS. In accordance with the NINDS Benchmarks for Epilepsy Research, completion of this will result in 1) improved identification of tumors that are most likey to respond to anti-glutaminergic treatments, 2) identification of genes and pathways associated with epilepsy; 3) advancement in the understanding of the epileptogenic process of TAS.