© 1994 Oxford University Press
OTHER |
The tuberous sclerosis gene on chromosome 9q34 acts as a growth suppressor
Department of Clinical Genetics, Addenbrooke's NHS Trust Cambridge Department of Pathology, University of Cambridge 1MRC Blood Group Unit Wolfson House, 4 Stephenson Way, London NW1 2HE, UK
*To whom correspondence should be addressed at: Department of Clinical Genetics, Box 134, Addenbrooke's NHS Trust, Cambridge CB2 2QQ, UK
Received June 23, 1994; Revised August 12, 1994; Accepted August 12, 1994
We have previously demonstrated allele loss in hamartomas from patients with tuberous sclerosis for markers spanning the tuberous sclerosis gene on chromosome 16p13.3 (TSC2). Germline deletions in the TSC2 gene have been shown in 5% of patients with tuberous sclerosis (TSC). These data support our hypothesis that the TSC2 gene acts as a growth suppressor gene, analogous to the traditional tumour suppressor gene. We now report a TSC hamartoma showing allele loss for markers on chromosome 9q34 in the region of the TSC1 gene. We studied six hamartomas from four sporadic and two familial cases of TSC, none of which showed allele loss for markers on chromosome 16p13.3. The hamartomas were paraffin embedded sections of three renal angiomyolipomas, two giant cell astrocytomas, and a cardiac rhabdomyoma. Eight markers were analysed, comprising from centromeric to telomeric ASS – D9S64 – D9S149 – ABO – D9S150 – DBH – D9S66 – D9S67. One angiomyolipoma showed allele loss for the markers ABO, DBH and D9S66, but not for D9S149 or D9S67. The patient was not informative for D9S150. The family structure did not permit the phase of the disease and marker alleles to be determined. These finding support the hypothesis that the TSC1 gene on 9q34, like the TSC2 gene, acts as a growth suppressor. The data would place the TSC1 gene between D9S149 and D9S67. Mapping of allele loss in hamartomas may help in the refinement of the location of the TSC1 locus.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. P Osborne, J. Merrifield, and F. J K O'Callaghan Tuberous sclerosis--what's new? Arch. Dis. Child., September 1, 2008; 93(9): 728 - 731. [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Juvet, F. X. McCormack, D. J. Kwiatkowski, and G. P. Downey Molecular Pathogenesis of Lymphangioleiomyomatosis: Lessons Learned from Orphans Am. J. Respir. Cell Mol. Biol., April 1, 2007; 36(4): 398 - 408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Nakase, K. Fukuda, Y. Chikashige, C. Tsutsumi, D. Morita, S. Kawamoto, M. Ohnuki, Y. Hiraoka, and T. Matsumoto A Defect in Protein Farnesylation Suppresses a Loss of Schizosaccharomyces pombe tsc2+, a Homolog of the Human Gene Predisposing to Tuberous Sclerosis Complex Genetics, June 1, 2006; 173(2): 569 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J C Lewis, H V Thomas, K C Murphy, and J R Sampson Genotype and psychological phenotype in tuberous sclerosis J. Med. Genet., March 1, 2004; 41(3): 203 - 207. [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Tee, R. Anjum, and J. Blenis Inactivation of the Tuberous Sclerosis Complex-1 and -2 Gene Products Occurs by Phosphoinositide 3-Kinase/Akt-dependent and -independent Phosphorylation of Tuberin J. Biol. Chem., September 26, 2003; 278(39): 37288 - 37296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Mackay, L. E. Becker, S. H. Chuang, H. Otsubo, N. A. Chuang, J. Rutka, B. Ben-Zeev, O. C. Snead III, and S. K. Weiss Malformations of cortical development with balloon cells: Clinical and radiologic correlates Neurology, February 25, 2003; 60(4): 580 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gogusev, I. Murakami, M. Doussau, L. Telvi, A. Stojkoski, P. Lesavre, and D. Droz Molecular Cytogenetic Aberrations in Autosomal Dominant Polycystic Kidney Disease Tissue J. Am. Soc. Nephrol., February 1, 2003; 14(2): 359 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Tee, D. C. Fingar, B. D. Manning, D. J. Kwiatkowski, L. C. Cantley, and J. Blenis Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling PNAS, October 15, 2002; 99(21): 13571 - 13576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Matsumoto, A. Bandyopadhyay, D. J. Kwiatkowski, U. Maitra, and T. Matsumoto Role of the Tsc1-Tsc2 Complex in Signaling and Transport Across the Cell Membrane in the Fission Yeast Schizosaccharomyces pombe Genetics, July 1, 2002; 161(3): 1053 - 1063. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Hodges, S. Li, J. Maynard, L. Parry, R. Braverman, J. P. Cheadle, J. E. DeClue, and J. R. Sampson Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin Hum. Mol. Genet., December 1, 2001; 10(25): 2899 - 2905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kobayashi, O. Minowa, Y. Sugitani, S. Takai, H. Mitani, E. Kobayashi, T. Noda, and O. Hino A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice PNAS, June 28, 2001; (2001) 151033798. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Kolomietz, J. Al-Maghrabi, S. Brennan, J. Karaskova, S. Minkin, J. Lipton, and J. A. Squire Primary chromosomal rearrangements of leukemia are frequently accompanied by extensive submicroscopic deletions and may lead to altered prognosis Blood, June 1, 2001; 97(11): 3581 - 3588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J O'Callaghan and J. P Osborne Recent advances: Advances in the understanding of tuberous sclerosis Arch. Dis. Child., August 1, 2000; 83(2): 140 - 142. [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. S. Pasumarthi, H. Nakajima, H. O. Nakajima, S. Jing, and L. J. Field Enhanced Cardiomyocyte DNA Synthesis During Myocardial Hypertrophy in Mice Expressing a Modified TSC2 Transgene Circ. Res., May 26, 2000; 86(10): 1069 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Carsillo, A. Astrinidis, and E. P. Henske Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis PNAS, May 23, 2000; 97(11): 6085 - 6090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Murthy, L. A. Haddad, N. Smith, D. Pinney, R. Tyszkowski, D. Brown, and V. Ramesh Similarities and differences in the subcellular localization of hamartin and tuberin in the kidney Am J Physiol Renal Physiol, May 1, 2000; 278(5): F737 - F746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J K O'CALLAGHAN, M. NOAKES, and J. P OSBORNE Renal angiomyolipomata and learning difficulty in tuberous sclerosis complex J. Med. Genet., February 1, 2000; 37(2): 156 - 157. [Full Text]
|
|
|
|
 |
|
 F. J K O'Callaghan Tuberous sclerosis BMJ, April 17, 1999; 318(7190): 1019 - 1020. [Full Text]
|
|
|
|
 |
|
 S. Johnson Rare diseases bullet 1: Lymphangioleiomyomatosis: clinical features, management and basic mechanisms Thorax, March 1, 1999; 54(3): 254 - 264. [Full Text]
|
|
|
|
|
|
F J K O'Callaghan, A C Clarke, H Joffe, B Keeton, R Martin, A Salmon, R D Thomas, and J P Osborne Tuberous sclerosis complex and Wolff-Parkinson-White syndrome Arch. Dis. Child., February 1, 1998; 78(2): 159 - 162. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. E. Schnur Tuberous Sclerosis: The Persistent Challenge of Clinical Diagnosis Arch Dermatol, December 1, 1995; 131(12): 1460 - 1462. [Abstract] [PDF]
|
|
|
|
|
|
T. Kobayashi, O. Minowa, Y. Sugitani, S. Takai, H. Mitani, E. Kobayashi, T. Noda, and O. Hino A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice PNAS, July 17, 2001; 98(15): 8762 - 8767. [Abstract] [Full Text] [PDF]
|
|