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.
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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).
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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
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