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Relaxation of imprinted genes in human cancer

Abstract

GENOMIC imprinting, or parental allele-specific expression of genes, has been demonstrated at the molecular level in insects and mice1,2 but not in man. Imprinting as a potential mechanism of human disease is suggested by paternal uniparental disomy of 11 p15 in Beckwith–Wiedemann syndrome3 and by maternal uniparental disomy of 15ql1–12 in Prader–Willi syndrome4. Beckwith–Wiedemann syndrome is characterized by multiorgan overgrowth and predisposition to embryonal tumours such as Wilms9 tumour of the kidney5. A loss of heterozygosity of 11 p15 is also frequently found in a wide variety of tumours, including Wilms' tumour and lung, bladder, ovarian, liver and breast cancers6–11; 11pl5 also directly suppresses tumour growth in vitro12. Two genes in this band, H19 and insulin-like growth factor-II (IGF2) undergo reciprocal imprinting in the mouse, with maternal expression of H19 (ref. 13) and paternal expression of IGF2 (ref. 14). Here we find that both of these genes show monoallelic expression in human tissues and, as in mouse, H19 is expressed from the maternal allele and IGF2 from the paternal allele. In contrast, 69% of Wilms' tumours not undergoing loss of heterozygosity at lip showed biallelic expression of one or both genes, suggesting that relaxation or loss of imprinting could represent a new epigenetic mutational mechanism in carcinogenesis.

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References

  1. Willison, K. Trends Genet. 7, 107–109 (1991).

    Article  CAS  Google Scholar 

  2. Holliday, R. Development suppl. 125–129 (1990).

  3. Henry, I. et al. Nature 351, 665–667 (1991).

    Article  ADS  CAS  Google Scholar 

  4. Nicholls, R. D., Knoll, J. H. M., Butler, M. G., Karam, S. & Lalande, N. Nature 342, 281–285 (1989).

    Article  ADS  CAS  Google Scholar 

  5. Pettenati, M. J. et al. Hum. Genet. 74, 143–154 (1986).

    Article  CAS  Google Scholar 

  6. Mannens, M. et al. Hum. Genet. 81, 41–48 (1988).

    Article  CAS  Google Scholar 

  7. Reeve, A. E., Sih, S. A., Raizis, A. M. & Feinberg, A. P. Molec. cell. Biol. 9, 1799–1803 (1989).

    Article  CAS  Google Scholar 

  8. Skinner, M. A., Vollmer, R., Huper, G., Abbott, P. & Inglebart, J. D. Cancer Res. 50, 2303–2306 (1990).

    CAS  PubMed  Google Scholar 

  9. Ali, I. U., Lidereau, R., Theillet, C. & Callahan, R. Science 238, 185–188 (1987).

    Article  ADS  CAS  Google Scholar 

  10. Fujimori, M. et al. Cancer Res. 51, 89–93 (1991).

    CAS  PubMed  Google Scholar 

  11. Ehlen, T. & Dubeau, L. Oncogene 5, 219–223 (1990).

    CAS  PubMed  Google Scholar 

  12. Koi, M. et al. Science (in the press).

  13. Bartolomei, M., Zemel, S. & Tilghman, S. M. Nature 351, 153–155 (1991).

    Article  ADS  CAS  Google Scholar 

  14. DeChiara, T. M., Robertson, E. J. & Efstratiadis, A. Cell 64, 849–859 (1991).

    Article  CAS  Google Scholar 

  15. Wiedemann, H. R. Eur. J. Pediatr. 141, 129 (1983).

    Article  Google Scholar 

  16. Zhang, Y. & Tycko, B. Nature Genet. 1, 40–44 (1992).

    Article  CAS  Google Scholar 

  17. Wagstaff, J. et al. Nature Genet. 1, 291–294 (1992).

    Article  CAS  Google Scholar 

  18. Haig, D. & Graham, C. Cell 64, 1045–1046 (1991).

    Article  CAS  Google Scholar 

  19. Davisson, M. T. et al. Cytogenet. Cell Genet. 58, 1152–1189 (1991).

    Article  Google Scholar 

  20. Ferguson-Smith, A. C., Cattanach, B. M., Barton, S. C., Beechey, C. V. & Surani, M. A. Nature 351, 667–670 (1991).

    Article  ADS  CAS  Google Scholar 

  21. Wadey, R. B. et al. Oncogene 5, 901–907 (1990).

    CAS  PubMed  Google Scholar 

  22. Little, M. H. et al. Proc. natn. Acad. Sci. U.S.A. 89, 4791–4795 (1992).

    Article  ADS  CAS  Google Scholar 

  23. Junien, C. Curr. Opin. Genet. Dev. 2, 431–438 (1992).

    Article  CAS  Google Scholar 

  24. Little, M., van Heyningen, V. & Hastie, N. Nature 351, 609–610 (1991).

    Article  ADS  CAS  Google Scholar 

  25. Hoovers, J. M. N., Dietrich, A. J. J. & Mannens, M. M. A. M. Lancet 339, 1228 (1992).

    Article  CAS  Google Scholar 

  26. Mannens, M. The Molecular Genetics of Wilms' Tumour and Associated Congenital Diseases (Univ. Amsterdam Press, Amsterdam, 1991).

    Google Scholar 

  27. Reeve, A. E., Eccles, M. R., Wilkins, R. J., Bell, G. I. & Millow, L. J. Nature 317, 258–260 (1985).

    Article  ADS  CAS  Google Scholar 

  28. Brannan, C. I., Dees, E. C., Ingram, R. S. & Tilghman, S. M. Molec. cell. Biol. 10, 28–36 (1990).

    Article  CAS  Google Scholar 

  29. Zemel, S., Bartolomei, M. S. & Tilghman, S. M., Nature Genet. 2, 61–65 (1992).

    Article  CAS  Google Scholar 

  30. Fearon, E. P. & Vogelstein, B. Cell 61, 759–767 (1990).

    Article  CAS  Google Scholar 

  31. Feinberg, A. P. & Vogelstein, B. Nature 301, 89–92 (1983).

    Article  ADS  CAS  Google Scholar 

  32. Jones, P. A. Cancer Res. 46, 461–466 (1986).

    CAS  PubMed  Google Scholar 

  33. Goelz, S. E., Vogelstein, B., Hamilton, S. R. & Feinberg, A. P. Science 228, 187–190 (1985).

    Article  ADS  CAS  Google Scholar 

  34. Beckwith, J. B., Kiviat, N. B. & Bonadio, J. F. Embryol. Dev. 1–36 (1990).

  35. Bennington, J. L., & Beckwith, J. B. Atlas of Tumor Pathology (Armed Forces Inst. Pathology, Washington, DC, 1975).

    Google Scholar 

  36. Tadokoro, K., Fujii, H., Inoue, T. & Yamada, M. Nucleic Acids Res. 19, 6967 (1991).

    Article  CAS  Google Scholar 

  37. Saiki, R. K. et al. Science 230, 1350–1354 (1985).

    Article  ADS  CAS  Google Scholar 

  38. Church, G. M. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 81, 1991–1995 (1984).

    Article  ADS  CAS  Google Scholar 

  39. Shuldiner, A. R., Tanner, K., Moore, C. A. & Roth, J. BioTechniques 11, 760–763 (1991).

    CAS  Google Scholar 

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Rainier, S., Johnson, L., Dobry, C. et al. Relaxation of imprinted genes in human cancer. Nature 362, 747–749 (1993). https://doi.org/10.1038/362747a0

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