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Somatic deletion and duplication of genes on chromosome 11 in Wilms' tumours

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.

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References

  1. Miller, R. W., Fraumeni, J. F. & Mannin, M. D. New Engl. J. Med. 270, 922–927 (1964).

    Article  CAS  Google Scholar 

  2. Riccardi, V. M., Sujansky, E., Smith, A. C. & Francke, U. Pediatrics 61, 604–610 (1978).

    CAS  Google Scholar 

  3. Knudson, A. G. Jr J. natn. Cancer Inst. 48, 313–324 (1972).

    Google Scholar 

  4. Kaneko, Y., Egues, M. C. & Rowley, J. D. Cancer Res. 41, 4577–4578 (1981).

    CAS  PubMed  Google Scholar 

  5. Slater, R. M. & de Kraker, J. Cancer Genet. Cytogenet. 5, 237–245 (1982).

    Article  CAS  Google Scholar 

  6. Kaneko, Y., Kondo, K., Rowley, J. D., Moohr, J. W. & Mauer, H. S. Cancer Genet. Cytogenet. 10, 191–197 (1983).

    Article  CAS  Google Scholar 

  7. Cavenee, W. K. et al. Nature 305, 779–784 (1983).

    Article  ADS  CAS  Google Scholar 

  8. deMartinville, B. & Francke, U. Nature 305, 641–643 (1983).

    Article  ADS  CAS  Google Scholar 

  9. Huerre, C., Despoisse, S., Gilgenkrantz, S., Lenoir, G. M. & Junien, C. Nature 305, 638–641 (1983).

    Article  ADS  CAS  Google Scholar 

  10. Harper, M. E., Ullrich, A. & Saunders, G. A. proc. natn. Acad. Sci. U.S.A. 75, 4458–4460 (1981).

    Article  ADS  Google Scholar 

  11. Morton, C. C., Kirsch, I. R., Taub, R. A., Orkin, S. H. & Brown, J. A. Am. J. hum Genet. (in the press).

  12. Jhanwar, S. C., Neel, B. G., Hayward, W. S. & Changanti, R. S. K. Proc. natn. Acad. Sci. U.S.A. 80, 4794–4797 (1983).

    Article  ADS  CAS  Google Scholar 

  13. Mayer, H., Breyel, E., Bostock, C. & Schmidke, J. Hum. Genet. 64, 283–285 (1983).

    Article  CAS  Google Scholar 

  14. Fearon, E., Antonarakis, S. E., Meyers, D. A. & Levine, M. A. Am. J. hum. Genet. (in the press).

  15. Jeffreys, A. J. Cell. 18, 1–10 (1979).

    Article  CAS  Google Scholar 

  16. Phillips, J. A. et al. Proc. natn. Acad. Sci. U.S.A. 77, 2853–2856 (1980).

    Article  ADS  CAS  Google Scholar 

  17. Bell, G. I., Selby, M. J. & Rutter, W. J. Nature 295, 31–35 (1982).

    Article  ADS  CAS  Google Scholar 

  18. Rotwein, P. S. et al. New Engl. J. Med. 308, 65–71 (1983).

    Article  CAS  Google Scholar 

  19. Goldfarb, M. P., Shimigu, K., Perucho, M. & Wigler, M. H. Nature 296, 404–409 (1982).

    Article  ADS  CAS  Google Scholar 

  20. Capon, D. J., Chen, E. Y., Levinson, A. D., Seeburg, P. H. & Goeddel, D. V. Nature 302, 33–37 (1983).

    Article  ADS  CAS  Google Scholar 

  21. Antonarakis, S. E. et al. Proc. natn. Acad. Sci. U.S.A. 80, 6615–6619 (1983).

    Article  ADS  CAS  Google Scholar 

  22. George, D. L., Phillips, J. A., Francke, U. & Seeburg, P. H. Hum. Genet. 57, 138–141 (1981).

    Article  CAS  Google Scholar 

  23. Hardin, J. W., Riser, M. E., Trent, J. M. & Kohler, P. O. Proc. natn. Acad. Sci. U.S.A. 80, 6282–6285 (1983).

    Article  ADS  CAS  Google Scholar 

  24. 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).

    Google Scholar 

  25. Phillips, J. A. et al. J. clin. Invest. 70, 489–495 (1982).

    Article  Google Scholar 

  26. Prochownik, E. V. et al. New Engl. J. Med. 308, 1549–1552 (1983).

    Article  CAS  Google Scholar 

  27. Orkin, S. H., Goldman, D. & Sallan, S. E. Nature 309, 172–174 (1984).

    Article  ADS  CAS  Google Scholar 

  28. Gross-Bellard, M., Oudet, P. & Chambon, P. Eur. J. Biochem. 36, 32–38 (1973).

    Article  CAS  Google Scholar 

  29. Burton, K. Biochem. J. 62, 315–323 (1956).

    Article  CAS  Google Scholar 

  30. Southern, E. M. J. molec. Biol. 98, 503–517 (1975).

    Article  CAS  Google Scholar 

  31. Wahl, G. M., Stern, M. & Stark, G. R. Proc. natn. Acad. Sci. U.S.A. 76, 3683–3687 (1979).

    Article  ADS  CAS  Google Scholar 

  32. Wilson, J. T. et al. Nucleic Acids Res. 5, 562–581 (1978).

    Article  Google Scholar 

  33. Shih, C. & Weinberg, R. A. Cell 29, 161–169 (1982).

    Article  CAS  Google Scholar 

  34. Hendy, G. N., Kronenberg, H. M., Potts, J. T. & Rich, A. Proc. natn. Acad. Sci. U.S.A. 78, 7365–7369 (1981).

    Article  ADS  CAS  Google Scholar 

  35. Feinberg, A. P. & Vogelstein, B. Analyt. Biochem. 132, 6–13 (1983).

    Article  CAS  Google Scholar 

  36. Feinberg, A. P. & Vogelstein, B. Analyt. Biochem. 137, 266–267 (1984).

    Article  CAS  Google Scholar 

  37. Peden, K., Mounts, P. & Hayward, G. S. Cell 31, 71–80 (1982).

    Article  CAS  Google Scholar 

  38. Swanstrom, R. & Shank, P. Analyt. Biochem. 86, 184–192 (1978).

    Article  CAS  Google Scholar 

  39. Martial, J. A., Hallewell, R. A., Baxter, J. D. & Goodman, H. M. Science 205, 602–607 (1979).

    Article  ADS  CAS  Google Scholar 

  40. Fiddes, J. C. & Goodman, H. M. Nature 281, 351–356 (1979).

    Article  ADS  CAS  Google Scholar 

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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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