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: 9036472
• 负责人: Jong Woo Lee
• 金额: $ 8.88万
• 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 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9036472
• 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; Health; 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; novel therapeutics; overexpression; programs; 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.

 描述（由申请人提供）：大约一半的脑肿瘤患者存在肿瘤相关癫痫发作（TAS），并导致这些患者的生活质量显着下降。了解 TAS 的潜在机制，对于新疗法的开发至关重要。 ，受到其多因素性质的阻碍，因为成像和基因组特征都发挥着关键作用，同时检查神经成像和基因表达在 TAS 中的贡献比评估其中任何一个更容易发现 TAS 的生物学相关机制。这项研究的中心假设是肿瘤基因表达以大脑区域特异性的方式与 TAS 相关。这项研究将利用来自精心策划的公共存储库的基因组和 MRI 数据：癌症基因组图谱 (TCGA)，肿瘤分子 BRA 数据库（REMBRANDT，用于验证）和癌症成像档案库 (TCIA) 具体目标是：1) 使用 TCGA 数据集，识别差异表达的基因和基因集。 2) 使用 TCGA 和 TCIA 数据集，描述基因表达与 TAS 显着相关的大脑区域。通过谷氨酸失调建立的 TAS 机制将评估其他新基因和基因组的差异表达，新开发的基因表达统计图像映射工具将用于分析大脑中的情况。 SLC7A11 和其他关键基因的表达与 TAS 显着相关，假设与额叶区域相比，SLC7A11 表达与颞叶中的 TAS 具有更高的相关性，因为与肿瘤相关。根据 NINDS，结合基因表达和成像信息是一种新颖且有效的表征 TAS 的方法。癫痫研究基准，完成这项工作将导致 1) 改进对最有可能对抗谷氨酰胺能治疗产生反应的肿瘤的识别，2) 识别与癫痫相关的基因和途径；3) 增进对癫痫发生过程的理解；塔斯马尼亚州。

项目成果

Glioma genetic profiles associated with electrophysiologic hyperexcitability.

神经胶质瘤遗传特征与电生理过度兴奋相关。

• 发表时间: 2023-02-24
• 作者: Tobochnik, Steven;Dorotan, Maria Kristina C;Ghosh, Hia S;Lapinskas, Emily;Vogelzang, Jayne;Reardon, David A;Ligon, Keith L;Bi, Wenya Linda;Smirnakis, Stelios M;Lee, Jong Woo
• 通讯作者: Lee, Jong Woo

Antiepileptic Drug Management in Hospitalized Epilepsy Patients With Nil Per Os Diets: A Retrospective Review.

住院癫痫患者零腹饮食的抗癫痫药物管理：回顾性回顾。

• 发表时间: 2019-04
• 作者: Bank, Anna M;Lee, Jong Woo;Ehlert, Alexa N;Berkowitz, Aaron L
• 通讯作者: Berkowitz, Aaron L

The role of cEEG as a predictor of patient outcome and survival in patients with intraparenchymal hemorrhages.

cEEG 作为脑实质出血患者预后和生存预测的作用。

• 发表时间: 2018-10
• 作者: Purandare, Mallika;Ehlert, Alexa N;Vaitkevicius, Henri;Dworetzky, Barbara A;Lee, Jong Woo
• 通讯作者: Lee, Jong Woo

Glioma genetic profiles associated with electrophysiologic hyperexcitability.

神经胶质瘤遗传特征与电生理过度兴奋相关。

• 发表时间: 2024-02-02
• 影响因子: 15.9
• 作者: Tobochnik, Steven;Dorotan, Maria Kristina C;Ghosh, Hia S;Lapinskas, Emily;Vogelzang, Jayne;Reardon, David A;Ligon, Keith L;Bi, Wenya Linda;Smirnakis, Stelios M;Lee, Jong Woo
• 通讯作者: Lee, Jong Woo