Aronica E, Boer K, Becker A, Redeker S, Spliet W G M, van Rijen P C, Wittink F, Breit T, Wadman W J, Lopes da Silva F H, Troost D, Gorter J A
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Neuroscience. 2008 Jan 2;151(1):272-92. doi: 10.1016/j.neuroscience.2007.10.036. Epub 2007 Nov 12.
Gangliogliomas (GG) constitute the most frequent tumor entity in young patients undergoing surgery for intractable epilepsy. The histological composition of GG, with the presence of dysplastic neurons, corroborates their maldevelopmental origin. However, their histogenesis, the pathogenetic relationship with other developmental lesions, and the molecular alterations underlying the epileptogenicity of these tumors remain largely unknown. We performed gene expression analysis using the Affymetrix Gene Chip System (U133 plus 2.0 array). We used GENMAPP and the Gene Ontology database to identify global trends in gene expression data. Our analysis has identified various interesting genes and processes that are differentially expressed in GG when compared with normal tissue. The immune and inflammatory responses were the most prominent processes expressed in GG. Several genes involved in the complement pathway displayed a high level of expression compared with control expression levels. Higher expression was also observed for genes involved in cell adhesion, extracellular matrix and proliferation processes. We observed differential expression of genes as cyclin D1 and cyclin-dependent kinases, essential for neuronal cell cycle regulation and differentiation. Synaptic transmission, including GABA receptor signaling was an under-expressed process compared with control tissue. These data provide some suggestions for the molecular pathogenesis of GG. Furthermore, they indicate possible targets that may be investigated in order to dissect the mechanisms of epileptogenesis and possibly counteract the epileptogenic process in these developmental lesions.
神经节胶质瘤（GG）是接受顽固性癫痫手术的年轻患者中最常见的肿瘤类型。GG的组织学组成，包括发育异常的神经元，证实了它们起源于发育异常。然而，它们的组织发生、与其他发育性病变的致病关系以及这些肿瘤致痫性的分子改变在很大程度上仍不清楚。我们使用Affymetrix基因芯片系统（U133 plus 2.0阵列）进行基因表达分析。我们使用GENMAPP和基因本体数据库来识别基因表达数据中的整体趋势。我们的分析确定了与正常组织相比，在GG中差异表达的各种有趣的基因和过程。免疫和炎症反应是GG中表达最突出的过程。与对照表达水平相比，参与补体途径的几个基因显示出高水平的表达。在参与细胞粘附、细胞外基质和增殖过程的基因中也观察到较高的表达。我们观察到细胞周期蛋白D1和细胞周期蛋白依赖性激酶等基因的差异表达，这些基因对神经元细胞周期调节和分化至关重要。与对照组织相比，包括GABA受体信号传导在内的突触传递是一个表达不足的过程。这些数据为GG的分子发病机制提供了一些线索。此外，它们指出了可能的研究靶点，以便剖析致痫机制，并可能对抗这些发育性病变中的致痫过程。
