Apparent preferential loss of heterozygosity atTSC2 overTSC1 chromosomal region in tuberous sclerosis hamartomas
- 1 January 1996
- journal article
- research article
- Published by Wiley in Genes, Chromosomes and Cancer
- Vol. 15 (1) , 18-25
- https://doi.org/10.1002/(sici)1098-2264(199601)15:1<18::aid-gcc3>3.0.co;2-7
Abstract
To investigate the molecular mechanisms of tuberous sclerosis (TSC) histopathologic lesions, we have tested for loss of heterozygosity the two TSC loci (TSC1 and TSC2) and seven tumor suppressor gene-containing regions (TP53, NF1, NF2, BRCA1, APC, VHL, and MLM) in 20 hamartomas from 18 TSC patients. Overall, eight angiomyolipomas, eight giant cell astrocytomas, one cortical tuber, and three rhabdomyomas were analyzed. Loss of heterozygosity at either TSC locus was found in a large fraction of the informative patients, both sporadic (7/14) and familial (1/4). Interestingly, a statistically significant preponderance of loss of heterozygosity at TSC2 was observed in the sporadic group (P < 0.01). Among the possible explanations considered, the bias in the selection for TSC patients with the most severe organ impairment seems particularly appealing. According to this view, a TSC2 defect might confer a greater risk for early kidney failure or, possibly, a more rapid growth of a giant cell astrocytoma. None of the seven antioncogenes tested showed loss of heterozygosity, indicating that the loss of either TSC gene product may be sufficient to promote hamartomatous cell growth. Finally, the observation of loss of heterozygosity at different markers in an astrocytoma and in an angiomyolipoma from the same patient might suggest the multifocal origin of the second-hit mutation.Keywords
This publication has 22 references indexed in Scilit:
- The CEPH consortium linkage map of human chromosome 16Genomics, 1995
- A germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancerNature Genetics, 1995
- The 1993–94 Généthon human genetic linkage mapNature Genetics, 1994
- Two loci for Tuberous Sclerosis: one on 9q34 and one on 16p13Annals of Human Genetics, 1994
- A Cell Cycle Regulator Potentially Involved in Genesis of Many Tumor TypesScience, 1994
- Report of the Second International Workshop on Human Chromosome 9 Mapping 1993Cytogenetic and Genome Research, 1993
- Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney diseaseNature Genetics, 1992
- Report of the Diagnostic Criteria Committee of the National Tuberous Sclerosis AssociationJournal of Child Neurology, 1992
- Evidence for genetic heterogeneity in tuberous sclerosis.Journal of Medical Genetics, 1989
- LINKAGE OF TUBEROUS SCLEROSIS TO ABO BLOOD GROUPThe Lancet, 1987