Abstract
Recent studies have shown that normal cellular sequences on chromosome 13 are lost during the development of retinoblastomas1 and that sequences on chromosome 11 are similarly lost during the development of Wilms' kidney tumours2–5 and embryonal tumours6. Cells from these tumours have been found to contain either the paternal or maternal copies of loci on the affected chromosome, but not both. Thus, the somatic loss of heterozygosity for sequences on chromosome 13 or 11 is hypothesized to result in homozygosity for a recessive mutant allele on these chromosomes1, and in this way the chromosomal loss may contribute to the development of these tumours. We sought to investigate whether similar losses of heterozygosity for chromosome 11 sequences occurred in a common adult tumour. We chose to analyse bladder cancers, since such cancers are common in the adult population and are derived from urogenital tissue, as are Wilms' tumours. We examined constitutional and tumour genotypes at loci on the short arm of chromosome 11 (11p) in 12 patients with transitional cell carcinomas. In five tumours, we observed the somatic loss of genes on 11p resulting in homozygosity or hemizygosity of the non-deleted alleles in the tumour cells. Our results show that the frequency of loss of 11p sequences in bladder cancer approaches that seen in Wilms' tumour (42% compared with 55%)7, and suggest that recessive genetic changes involving sequences on 11p may contribute to the development of bladder neoplasms.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Cavenee, W. K. et al. Nature 305, 779–784 (1983).
Koufos, A. et al. Nature 309, 170–172 (1984).
Orkin, S. H., Goldman, D. S. & Sallan, S. E. Nature 309, 172–174 (1984).
Reeve, A. E. et al. Nature 309, 174–176 (1984).
Fearon, E. R., Vogelstein, B. & Feinberg, A. P. Nature 309, 176–178 (1984).
Koufos, A. et al. Nature 316, 330–334 (1985).
Solomon, E., 309, 111–112 (1984).
Fisher, J. H. et al. Somat. Cell Molec. Genet. 10, 455–464 (1984).
Capon, D. J., Charen, E. Y., Levinson, A. D., Seeburg, P. H. & Goeddel, D. V. Nature 302, 33–37 (1983).
Harper, M. E., Ullrich, A. & Saunders, G. A. Proc. natn. Acad. Sci. U.S.A. 75, 4458–4460 (1981).
Bell, G. I., Selby, M. J. & Rutter, W. J. Nature 295, 31–35 (1982).
Goelz, S. E., Hamilton, S. R. & Vogelstein, B. Biochem. biophys. Res. Commun. 130, 118–126 (1985).
Adcock, M. W. & O'Brien, W. P. J. biol. Chem. 259, 13471–13476 (1984).
Wyman, A. R. & White, R. Proc. natn. Acad. Sci. U.S.A. 77, 6754–6758 (1980).
Gibos, Z., Prout, G. R., Connally, J. G., Pontes, J. E. & Sandberg, A. A. Cancer Res. 44, 1257–1264 (1984).
Atkin, N. B. & Baker, M. C. Cancer Genet. Cytogenet. 15, 253–268 (1985).
Kondo, K., Chilcote, R. R., Mauver, H. S. & Rowley, J. D. Cancer Res. 44, 5376–5381 (1984).
Comings, D. E. Proc. natn. Acad. Sci. U.S.A. 70, 3324–3328 (1973).
Knudson, A. G. & Strong, L. C. J. natn. Cancer Inst. 48, 313–324 (1972).
Dryja, T. P. et al. New Engl. J. Med. 310, 550–553 (1984).
Burton, K. Biochem. J. 62, 315–323 (1956).
Southern, E. M. J. molec. Biol. 98, 503–517 (1975).
Wahl, G. M., Stern, M. & Stark, G. R. Proc. natn. Acad. Sci. U.S.A. 76, 3683–3687 (1979).
Shih, C. & Weinberg, R. A. Cell 29, 161–167 (1982).
Rotwein, P. S. et al. New Engl. J. Med. 308, 65–71 (1983).
Feinberg, A. P. & Vogelstein, B. Analyt. Biochem. 132, 6–13 (1983).
Feinberg, A. P. & Vogelstein, B. Analyt. Biochem. 137, 266–267 (1984).
Peden, K., Mounts, P. & Hayward, G. S. Cell 31, 71–80 (1982).
Swanstrom, R. & Shank, P. Analyt. Biochem. 86, 184–192 (1978).
Cavenee, W., Leach, R., Mohandas, T., Pearson, P. & White, R. Am. J. hum. Genet. 36, 10–24 (1984).
Prochownik, E. V. et al. New Engl. J. Med. 308, 1549–1552 (1983).
Robbins, S. L., Cotran, R. S. & Kumar, V., Pathologic Basis of Disease 3rd end 1070–1076 (Saunders, Philadelphia, 1984).
Fearon, E. R. et al. Hum. Genet. 70, 207–210 (1985).
Skolnick, M. A., Willard, H. F. & Menlove, L. A. Cytogenet. Cell Genet. 37, 210–273 (1984).
Francomano, C., Nunez, A. M., Yamada, Y. & Phillips, J. A. Am. J. hum. Genet. 37S 404 (1984).
Phillips, J. A. et al. J. clin. invest. 70, 489–495 (1982).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fearon, E., Feinberg, A., Hamilton, S. et al. Loss of genes on the short arm of chromosome 11 in bladder cancer. Nature 318, 377–380 (1985). https://doi.org/10.1038/318377a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/318377a0
This article is cited by
-
Hints on ATGL implications in cancer: beyond bioenergetic clues
Cell Death & Disease (2018)
-
Methylation of p16INK4A and p57KIP2 are involved in the development and progression of gastric MALT lymphomas
Modern Pathology (2006)
-
Mutational activation of BRAF is not a major event in sporadic childhood papillary thyroid carcinoma
Modern Pathology (2005)
-
BRAF mutations in anaplastic thyroid carcinoma: implications for tumor origin, diagnosis and treatment
Modern Pathology (2004)
-
Transcript map and complete genomic sequence for the 310 kb region of minimal allele loss on chromosome segment 11p15.5 in non-small-cell lung cancer
Oncogene (2001)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.