Gene expression profile analysis of epilepsy-associated gangliogliomas.
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.
Aronica
E
E
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. e.aronica@amc.uva.nl
Boer
K
K
Becker
A
A
Redeker
S
S
Spliet
W G M
WG
van Rijen
P C
PC
Wittink
F
F
Breit
T
T
Wadman
W J
WJ
Lopes da Silva
F H
FH
Troost
D
D
Gorter
J A
JA
D000328:Adult; D001932:Brain Neoplasms / Q000150:complications* / Q000235:genetics*; D002448:Cell Adhesion / Q000187:drug effects; D003165:Complement System Proteins / Q000096:biosynthesis / Q000235:genetics; D017931:DNA Primers; D004827:Epilepsy / Q000150:complications* / Q000235:genetics*; D005109:Extracellular Matrix / Q000378:metabolism; D018303:Ganglioglioma / Q000150:complications* / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D016707:Tissue Fixation; D051153:Wnt Proteins / Q000096:biosynthesis; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D017931:DNA Primers; D012334:RNA, Neoplasm; D051153:Wnt Proteins; D005680:gamma-Aminobutyric Acid; D003165:Complement System Proteins