Abstract
One of the most provocative findings in tumour biology is the relationship between chromosomal changes and embryonal cancers in children. For example, children with the rare paediatric syndrome AGR triad (aniridia, genito-urinary abnormalities and mental retardation) often develop Wilms' tumours at a very early age1 and carry a germ-line deletion on the short arm of chromosome 11 (11p13) 2. It has been suggested that the germ-line deletion 11p is the first of two or more steps to cancer in AGR children2. If this were true, one might expect a similar deletion to arise somatically in the far more common isolated Wilms' tumours of children without AGR, as suggested by Knudson3 from epidemiological data. However, a chromosomal deletion on 11p was observed in only two of five such cases4,5, while it was absent or seen inconsistently in others5,6. We have now used a molecular genetic approach to determine whether Wilms' tumour cells possess somatic alterations at 11p loci. We have found somatic deletions of specific genes in four of six Wilms' tumours. Surprisingly, in all four cases, the deletions were associated with duplications leading to homozygosity of the non-deleted alleles in the tumour cells. As analogous observations were recently reported in retinoblastoma7, the genetic events reported here may underlie the development of many such embryonal tumours in children.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Rent or buy this article
Get just this article for as long as you need it
$39.95
Prices may be subject to local taxes which are calculated during checkout
References
Miller, R. W., Fraumeni, J. F. & Mannin, M. D. New Engl. J. Med. 270, 922–927 (1964).
Riccardi, V. M., Sujansky, E., Smith, A. C. & Francke, U. Pediatrics 61, 604–610 (1978).
Knudson, A. G. Jr J. natn. Cancer Inst. 48, 313–324 (1972).
Kaneko, Y., Egues, M. C. & Rowley, J. D. Cancer Res. 41, 4577–4578 (1981).
Slater, R. M. & de Kraker, J. Cancer Genet. Cytogenet. 5, 237–245 (1982).
Kaneko, Y., Kondo, K., Rowley, J. D., Moohr, J. W. & Mauer, H. S. Cancer Genet. Cytogenet. 10, 191–197 (1983).
Cavenee, W. K. et al. Nature 305, 779–784 (1983).
deMartinville, B. & Francke, U. Nature 305, 641–643 (1983).
Huerre, C., Despoisse, S., Gilgenkrantz, S., Lenoir, G. M. & Junien, C. Nature 305, 638–641 (1983).
Harper, M. E., Ullrich, A. & Saunders, G. A. proc. natn. Acad. Sci. U.S.A. 75, 4458–4460 (1981).
Morton, C. C., Kirsch, I. R., Taub, R. A., Orkin, S. H. & Brown, J. A. Am. J. hum Genet. (in the press).
Jhanwar, S. C., Neel, B. G., Hayward, W. S. & Changanti, R. S. K. Proc. natn. Acad. Sci. U.S.A. 80, 4794–4797 (1983).
Mayer, H., Breyel, E., Bostock, C. & Schmidke, J. Hum. Genet. 64, 283–285 (1983).
Fearon, E., Antonarakis, S. E., Meyers, D. A. & Levine, M. A. Am. J. hum. Genet. (in the press).
Jeffreys, A. J. Cell. 18, 1–10 (1979).
Phillips, J. A. et al. Proc. natn. Acad. Sci. U.S.A. 77, 2853–2856 (1980).
Bell, G. I., Selby, M. J. & Rutter, W. J. Nature 295, 31–35 (1982).
Rotwein, P. S. et al. New Engl. J. Med. 308, 65–71 (1983).
Goldfarb, M. P., Shimigu, K., Perucho, M. & Wigler, M. H. Nature 296, 404–409 (1982).
Capon, D. J., Chen, E. Y., Levinson, A. D., Seeburg, P. H. & Goeddel, D. V. Nature 302, 33–37 (1983).
Antonarakis, S. E. et al. Proc. natn. Acad. Sci. U.S.A. 80, 6615–6619 (1983).
George, D. L., Phillips, J. A., Francke, U. & Seeburg, P. H. Hum. Genet. 57, 138–141 (1981).
Hardin, J. W., Riser, M. E., Trent, J. M. & Kohler, P. O. Proc. natn. Acad. Sci. U.S.A. 80, 6282–6285 (1983).
Naylor, S. L., Chin, W. W., Goodman, H. M. & Sakaguchi, A. Y. International Human Gene Mapping Workshop VII Program (ed. Sparkes, R. S.) 213 (Abstr.) (University of California, Los Angeles, 1983).
Phillips, J. A. et al. J. clin. Invest. 70, 489–495 (1982).
Prochownik, E. V. et al. New Engl. J. Med. 308, 1549–1552 (1983).
Orkin, S. H., Goldman, D. & Sallan, S. E. Nature 309, 172–174 (1984).
Gross-Bellard, M., Oudet, P. & Chambon, P. Eur. J. Biochem. 36, 32–38 (1973).
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).
Wilson, J. T. et al. Nucleic Acids Res. 5, 562–581 (1978).
Shih, C. & Weinberg, R. A. Cell 29, 161–169 (1982).
Hendy, G. N., Kronenberg, H. M., Potts, J. T. & Rich, A. Proc. natn. Acad. Sci. U.S.A. 78, 7365–7369 (1981).
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).
Martial, J. A., Hallewell, R. A., Baxter, J. D. & Goodman, H. M. Science 205, 602–607 (1979).
Fiddes, J. C. & Goodman, H. M. Nature 281, 351–356 (1979).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fearon, E., Vogelstein, B. & Feinberg, A. Somatic deletion and duplication of genes on chromosome 11 in Wilms' tumours. Nature 309, 176–178 (1984). https://doi.org/10.1038/309176a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/309176a0
This article is cited by
-
Submicroscopic deletion of 5q involving tumor suppressor genes (CTNNA1, HSPA9) and copy neutral loss of heterozygosity associated with TET2 and EZH2 mutations in a case of MDS with normal chromosome and FISH results
Molecular Cytogenetics (2014)
-
Progress of fundamental research in Wilms' tumor
Urological Research (1997)
-
A common region of loss of heterozygosity in Wilms' tumor and embryonal rhabdomyosarcoma distal to the D11S988 locus on chromosome 11p15.5
Human Genetics (1996)
-
Hereditary cancer: Two hits revisited
Journal of Cancer Research and Clinical Oncology (1996)
-
Tumor Suppressor Genes: Prospects for Cancer Therapies
Nature Biotechnology (1995)
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.