CONFINEMENT OF CHROMOSOMAL INSTABILITY TO THE [italic]TSC1 [/italic]TUMOR SUPPRESSOR GENE LOCUS IN FOCAL CORTICAL DYSPLASIA OF TAYLOR[apos]S BALLOON CELL TYPE
Abstract number :
2.057
Submission category :
Year :
2003
Submission ID :
3752
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Jana Fassunke, Ingmar Blümcke, Rainer Lahl, Heinz W. Pannek, Ingrid Tuxhorn, Christian E. Elger, Johannes Schramm, Micaela Mathiak, Otmar D. Wiestler, Albert J. Becker Dept of Neuropathology, University of Bonn Medical Center; Dept of Neuropathology, Univ
Focal cortical dysplasias (FCD) represent a frequent finding in patients with chronic intractable epilepsy. Neuropathological hallmarks are localized dyslamination of the neocortex and adjacent white matter. Balloon cells, similar to those occuring in cortical tubers of patients with tuberous sclerosis (TSC) are observed in numerous patients (FCD[sub]bc[/sub]). Recent findings indicate an accumulation of TSC1 polymorphisms in FCD[sub]bc[/sub] that frequently co-occur with loss of heterozygosity (LOH) and/or variability of microsatellite repeats at the TSC1 locus on chromosome 9q. In order to determine whether chromosomal instability in FCD[sub]bc[/sub] is pronounced at the TSC1 locus or a more genome wide phenomenon, in 14 FCD[sub]bc[/sub] lesions we have analyzed a set of five microsatellite markers with random genomic distribution, i.e. BAT25 (4q12), BAT26 (2p16.3-p2), D2S123 (2p16), D17S250 (17q11.2-q12) and D5S346 (5q21/22). DNA from laser-microdissected individual cells, i.e. balloon cells vs. control neurons obtained from adjacent normal cortex served as starting material for PCR and subsequent fluorescent fragment length gel electrophoresis.
This analysis resulted in sporadic observations of LOH and MSI at genomic loci on 2p and 17q in the present FCD[sub]bc[/sub] series. No microsatellite alterations occurred at 4q and 5q. Considering the substantial manifestation of genomic instability events at the TSC1 locus on 9q in FCD[sub]bc[/sub], the present data point towards LOH and MSI to be focused at the TSC1 locus in FCD[sub]bc[/sub].
Our findings indicate that the molecular pathogenesis of FCD[sub]bc[/sub] is associated with TSC1.
[Supported by: DFG (SFB TR3), BMBF (NGFN), and BONFOR]