Mutational analysis of TSC1 and TSC2 genes in gangliogliomas

Gangliogliomas constitute the most frequent tumour entity in patients with temporal lobe epilepsy. The characteristic histopathological admixture of g lial and neuronal elements, the Focal nature and their differentiated pheno type and benign biological behaviour suggest an origin from a developmental ly compromised or dysplastic precursor lesion. The present study analysed T SC1 and TSC2 genes as potential candidates involved in the pathogenesis of this intriguing neoplasm. Recent data suggest that both genes play a role i n cortical differentiation and growth control. DNA sequence analysis of TSC 1 and TSC2 was studied in 20 patients with gangliogliomas. Fifteen of these tumours (75%) carried polymorphisms in the TSC2 gene. The frequency of the se polymorphisms was significantly increased in intron 4 (12.5%) and exon 4 1 (15%,) compared to control individuals (8.1 and 6.5%, respectively. n=100 ). A somatic mutation in intron 32 of the TSC2 gene was encountered in one patient. In the TSC1 gene, seven polymorphisms occurred as a combination of base exchanges in exon 14 and intron 13. No mutations were observed in thi s gene. Laser microdissection and harvesting of individual neuronal and gli al elements identified the intron 32 mutation within the glial portion but not in dysplastic neurones of the tumour. The data demonstrate numerous pol ymorphisms as well as a novel TSC2 mutation in gangliogliomas from patients with chronic epilepsies. The selective detection of the TSC2 mutation with in the glial component of a ganglioglioma suggests that the glioma portion has undergone clonal evolution in this case.