Analysis of chromosomal instability in focal cortical dysplasia of Taylor’s balloon cell type

被引:0
作者
Jana Fassunke
Ingmar Blümcke
Rainer Lahl
Christian E. Elger
Johannes Schramm
Sabine Merkelbach-Bruse
Micaela Mathiak
Otmar D. Wiestler
Albert J. Becker
机构
[1] University of Bonn Medical Center,Department of Neuropathology
[2] University of Erlangen,Department of Neuropathology
[3] Epilepsy Center Bethel,Department of Neuropathology
[4] Clinic Mara,Department of Epileptology
[5] University of Bonn Medical Center,Department of Neurosurgery
[6] University of Bonn Medical Center,Department of Pathology
[7] University of Bonn Medical Center,undefined
来源
Acta Neuropathologica | 2004年 / 108卷
关键词
Balloon cell; Epilepsy; Microsatellite marker; Mismatch repair; Laser microdissection;
D O I
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中图分类号
学科分类号
摘要
Focal cortical dysplasias (FCD) represent a frequent finding in patients with chronic intractable epilepsy. Neuropathological hallmarks include localized dyslamination of the neocortex and neuronal heterotopias in white matter. Balloon cells, similar to those occurring in cortical tubers of patients with tuberous sclerosis (TSC) are observed in numerous patients. These lesions were classified as FCD type IIb (FCD IIb). Recent findings indicate an accumulation of TSC1 polymorphisms as well as loss of heterozygosity (LOH) and/or microsatellite instability (MSI) at the TSC1 locus on chromosome 9q in FCD IIb. Here, we tested the hypothesis of whether chromosomal instability constitutes a genome-wide phenomenon in this patient cohort. Seven microsatellite markers based on a reference panel recommended by the international workshop on microsatellite instability were analyzed in 14 surgical FCD IIb specimens. DNA from single laser-microdissected cells, i.e., balloon cells versus control neurons obtained from adjacent cortex was harvested for PCR amplification and subsequent fluorescent fragment length gel electrophoresis. Our analysis revealed only rare instances of LOH and MSI at genomic loci on 2p and 17q, whereas no alterations were found at informative markers on chromosomes 1p, 5q and 18q. In addition, no loss of repair protein expression (MSH2 or MLH1) has been identified in balloon cell nuclei of FCD IIb specimens. The present data suggest solitary LOH and MSI events at genomic localizations others than the TSC1 locus to occur in FCD IIb. Our findings lend further support to the hypothesis that the molecular pathogenesis of FCD IIb is associated with TSC1.
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页码:129 / 134
页数:5
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