Gene expression profile analyses of cortical dysplasia by cDNA arrays.
Cortical dysplasia (CD) is a well-recognized cause of intractable epilepsy, especially in children and is characterized histologically by derangements in cortical development and organization. The objective of this study was to expand the current knowledge of altered gene expression in CD as a first step towards in the identification of additional genes operative in the evolution of CD. Surgical specimens were obtained from eight patients (4 males and 4 females; age range 2-38 years; mean 15 years) with a pathologic diagnosis of CD. Nondysplastic temporal neocortex was obtained from a 2-year-old boy with intractable epilepsy and medial temporal lobe ganglioglioma. After total RNA isolation from frozen brain tissues, we carried out gene expression profiling using a cDNA expression array. Differences in gene expressions between CD and the nondysplastic neocortex were confirmed by semi-quantitative conventional reverse transcription-PCR. Three genes (recombination activating gene 1 (RAG1), heat shock 60 kDa protein 1 (HSP-60), and transforming growth factor beta1 (TGF beta1)) were found to be up-regulated more than two-fold in CD, whereas four genes (phosphoinositide-3-kinase regulatory subunit polypeptide 1 [p85 alpha] (PI3K), frizzled homolog 2 [Drosophila], Bcl-2/adenovirus E1B 19 kDa interacting protein (NIP3), and glia maturation factor beta (GMF beta)) were down-regulated to less than 50% of their normal levels. Interestingly, the majority of genes showing altered expression were associated with apoptosis. Our study demonstrates diverse changes in gene expression in CD. However, it remains to be shown which of these are causally related to the evolution of CD.
Kim
Seung-Ki
SK
Division of Pediatric Neurosurgery, Department of Neurosurgery, Seoul National University College of Medicine, Neurological Research Institute, SNUMRC, 28 Yongon-dong, Chongno-gu, Seoul 110-744, South Korea.
Wang
Kyu-Chang
KC
Hong
Soo Jin
SJ
Chung
Chun-Kee
CK
Lim
Su-Young
SY
Kim
Young-Yim
YY
Chi
Je G
JG
Kim
Chong Jai
CJ
Chung
You-Nam
YN
Kim
Hyun Jib
HJ
Cho
Byung-Kyu
BK
D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000473:pathology / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D015342:DNA Probes; D018076:DNA, Complementary / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D008279:Magnetic Resonance Imaging; D008297:Male; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015342:DNA Probes; D018076:DNA, Complementary; D012313:RNA