Nature Genetics
6, 193 - 196 (1994)
doi:10.1038/ng0294-193
Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patientsAndrew J. Green1, 2, Moyra Smith3
& John R.W. Yates1, 2
1Department of Clinical Genetics, Addenbrooke's Hospital Cambridge CB2 2QQ, UK
2Cambridge University Department of Pathology, Cambridge, CB2 1QP, UK
3University of California, Irvine, California 92717, USA Correspondence should be addressed to J.R.Y.W. Tuberous sclerosis (TSC) is an autosomal dominant condition with characteristic skin lesions, mental handicap, seizures and the development of hamartomas in the brain, heart, kidneys and other organs. Linkage studies have shown locus heterogeneity with a TSC gene mapped to chromosome 9q34 and a second, recently identified on 16p13.3. We have analysed DMA markers in eight hamartomas and one tumour from TSC patients and found allele loss on 16p13.3 in three angiomyolipomas, one cardiac rhabdomyoma, one cortical tuber and one giant cell astrocytoma. We suggest that the TSC gene on 16p13.3 functions like a tumour suppressor gene, in accordance with Knudsen's hypothesis.
REFERENCES
- Gomez, M.R. Phenotypes of the tuberous sclerosis complex with a revision of diagnostic criteria. Ann. N.Y. Acad. Sci. 615, 1−7 (1991). | PubMed | ChemPort |
- Fryer, A.E. et al. Evidence that the gene for tuberous sclerosis is on chromosome 9. Lancet 1, 659−661 (1987). | Article | PubMed | ISI | ChemPort |
- Burley, M.W. et al. Linkage Studies in Tuberous Sclerosis. Second International Chromosome 9 Workshop (1993). Cytogenet. cell Genet. (in the press).
- Smith, M. et al. Mapping of a gene determining tuberous sclerosis to human chromosome 11 q14−11 q23. Genomics 6, 105−114 (1991). | ISI |
- Fahsold, R., Rott, H.D. & Lorenz, P. A third gene locus for tuberous sclerosis is closely linked to the phenylalanine hydroxylase gene locus. Hum. Genet. 88, 85−90 (1991). | PubMed | ISI | ChemPort |
- Kandt, R.S. et al. Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease. Nature Genet. 2, 37−41 (1992). | Article | PubMed | ISI | ChemPort |
- Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 75, 1−11 (1993). | ISI |
- Legius, E., Marchuk, D.A., Collins, F.S. & GIover, T.W. Somatic deletion of the neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumour suppressor gene hypothesis. Nature Genet. 3, 122−126 (1993). | Article | PubMed | ISI | ChemPort |
- Seizinger, B.R. NF1: a prevalent cause of tumorigenesis in human cancers. Nature Genet. 3, 97−98 (1993). | Article | PubMed | ISI | ChemPort |
- Comings, D.E. Review of Gomez's 'Tuberous Sclerosis'. Am. J. hum. Genet. 32, 285−286 (1980).
- Knudsen, A.G.J. Mutation and cancer: Statistical study of retinoblastoma. Proc. natn. Acad. Sci. U.S.A. 68, 820−823 (1971).
- Smith, S.A., Easton, D.F., Evans, D.R.G. & Ponder, B.A.J. Allele losses in the region 17q12−21 in familial breast and ovarian cancer involve the wild type chromosome. Nature Genet. 2, 128−131 (1991). | ISI |
- Neumann, H.P.H. et al. Angiomyolipoma of the kidney and tuberous sclerosis. Am. J. hum. Genet. 51, A104 (1992).
- Webb, D.W., Thomas, R.D. & Osborne, J.P. Cardiac rhabdomyomas and their association with tuberous sclerosis. Arch. Dis. Childhood 68, 367−370 (1993). | ISI | ChemPort |
- Harding, C.O. & Pagon, R.A. Incidence of tuberous sclerosis in patients with cardiac rhabdomyoma. Am. J. med. Genet. 37, 443−446 (1990). | PubMed | ISI | ChemPort |
- Alper, J.C. & Holmes, J.B. The incidence and significance of birthmarks in a cohort of 4,641 newborns. Pediatr. Dermatol. 1, 56−68 (1983).
- Rocha, G. & Winkelman, R.K. Connective tissue nevus. Arch. Dermatol. 85, 722−729 (1962). | PubMed | ISI | ChemPort |
- Maniatis, T.M., Fritsch, E.F. & Sambrook, J. Molecular Cloning; A Laboratory Manual (Cold Spring Harbour Press, New York, 1982).
|
