Clonality of tuberous sclerosis harmatomas shown by non-random X-chromosome inactivation

Tuberous sclerosis (TSC) is an autosomal dominant condition characterised by tumour-like malformations (hamartomas) in the brain and other organs. A proportion of hamartomas from patients with TSC show loss of heterozygosity (LOH) for DNA markers in the region of either the TSC1 gene on chromosome 9...

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Bibliographic Details
Published in:Human genetics 1996-02, Vol.97 (2), p.240-243
Main Authors: Green, A J, Sepp, T, Yates, J R
Format: Article
Language:English
Subjects:
Angiomyolipoma - genetics
Base Sequence
Deoxyribonuclease HpaII
DNA, Neoplasm - analysis
DNA, Neoplasm - metabolism
Dosage Compensation, Genetic
Exons - genetics
Female
Fibroma - genetics
Humans
Kidney Neoplasms - genetics
Methylation
Molecular Sequence Data
Polymerase Chain Reaction - methods
Polymorphism, Genetic
Receptors, Androgen - genetics
Trinucleotide Repeats
Tuberous Sclerosis - genetics
X Chromosome
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Summary:Tuberous sclerosis (TSC) is an autosomal dominant condition characterised by tumour-like malformations (hamartomas) in the brain and other organs. A proportion of hamartomas from patients with TSC show loss of heterozygosity (LOH) for DNA markers in the region of either the TSC1 gene on chromosome 9q34 or the TSC2 gene on 16p13.3. This implies that these lesions are clonal. We have studied X-chromosome inactivation, as a marker of clonality, in 13 hamartomas from females with TSC. The hamartomas comprised five renal angiomyolipomas, three fibromas and seven other lesions. In previous studies, four of the lesions showed LOH. A polymerase chain reaction assay was used to analyse differential methylation of an HpaII restriction site adjacent to the androgen-receptor triplet-repeat polymorphism on Xq11-12. In 12 of the lesions, there was a skewed inactivation pattern with one X chromosome being fully methylated and the other unmethylated. Normal tissue showed a random pattern of inactivation. These data confirm that most TSC hamartomas are clonal in origin. This is an intriguing finding, since these lesions are composed of more than one cell type.
ISSN:0340-6717
1432-1203
DOI:10.1007/bf02265273