Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Hypomethylation distinguishes genes of some human cancers from their normal counterparts

Nature volume 301, pages 89–92 (1983)Cite this article

Abstract

It has been suggested that cancer represents an alteration in DNA, heritable by progeny cells, that leads to abnormally regulated expression of normal cellular genes; DNA alterations such as mutations1,2, rearrangements3–5 and changes in methylation6–8 have been proposed to have such a role. Because of increasing evidence that DNA methylation is important in gene expression (for review see refs 7, 9–11), several investigators have studied DNA methylation in animal tumours, transformed cells and leukaemia cells in culture8,12–30. The results of these studies have varied; depending on the techniques and systems used, an increase12–19, decrease20–24, or no change25–29 in the degree of methylation has been reported. To our knowledge, however, primary human tumour tissues have not been used in such studies. We have now examined DNA methylation in human cancer with three considerations in mind: (1) the methylation pattern of specific genes, rather than total levels of methylation, was determined; (2) human cancers and adjacent analogous normal tissues, unconditioned by culture media, were analysed; and (3) the cancers were taken from patients who had received neither radiation nor chemotherapy. In four of five patients studied, representing two histological types of cancer, substantial hypomethylation was found in genes of cancer cells compared with their normal counterparts. This hypomethylation was progressive in a metastasis from one of the patients.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. McCann, J. & Ames, B. N. Proc. natn. Acad. Sci. U.S.A. 73, 950–954 (1976).

    Article  ADS  CAS  Google Scholar 

  2. Meselson, M. & Russel, K. in Origins of Human Cancer Vol. 4 (eds Hiatt, H. H., Watson, J. D. & Winsten, J. A.) 1473–1481 (Cold Spring Harbor, New York, 1977).

    Google Scholar 

  3. Sager, R. Nature 282, 447–448 (1979).

    Article  ADS  CAS  Google Scholar 

  4. Cairns, J. Nature 289, 353–357 (1981).

    Article  ADS  CAS  Google Scholar 

  5. Humphreys, P. Nature 293, 146–148 (1981).

    Article  ADS  Google Scholar 

  6. Holliday, R. Br. J. Cancer 40, 513–521 (1979).

    Article  CAS  Google Scholar 

  7. Ehrich, M. & Wang, R. Y.-H. Science 212, 1350–1357 (1981).

    Article  ADS  Google Scholar 

  8. Sager, R. in Tumor Cell Heterogeneity: Origins and Implications (eds Owens, A. H., Coffey, D. S. & Baylin, S. B.) 411–423 (Academic, New York, 1982).

    Google Scholar 

  9. Razin, A. & Riggs, A. D. Science 210, 604–610 (1980).

    Article  ADS  CAS  Google Scholar 

  10. Doerfler, W. J. gen. Virol. 57, 1–20 (1981).

    Article  CAS  Google Scholar 

  11. Felsenfeld, G. & McGhee, J. Nature 296, 602–603 (1981).

    Article  ADS  Google Scholar 

  12. Silber, R. et al. Biochim. biophys. Acta 123, 638–640 (1966).

    Article  CAS  Google Scholar 

  13. Desai, L. S., Wulff, U. C. & Foley, G. E. Expl Cell Res. 65, 260–263 (1971).

    Article  CAS  Google Scholar 

  14. Shirakawa, S. & Saunders, G. F. Proc. Soc. exp. Biol. Med. 138, 369–372 (1971).

    Article  CAS  Google Scholar 

  15. Rubery, E. D. & Newton, A. A. Biochim. biophys. Acta 324, 24–36 (1973).

    Article  CAS  Google Scholar 

  16. Gunthert, U., Schweiger, M., Stupp, M. & Doerfler, W. Proc. natn. Acad. Sci. U.S.A. 73, 3923–3927 (1976).

    Article  ADS  CAS  Google Scholar 

  17. Fedorov, N. A., Kuzmichev, V. A., Kritsky, G. A. & Vinogradova, Yu. E. Biokhimiya 42, 1020–1023 (1977).

    CAS  Google Scholar 

  18. Nakhasi, H. L., Lynch, K. R., Dolan, K. P., Unterman, R. D. & Feigelson, P. Proc. natn. Acad. Sci. U.S.A. 78, 834–837 (1981).

    Article  ADS  CAS  Google Scholar 

  19. Nass, M. M. K. J. molec. Biol. 80, 155–175 (1973).

    Article  CAS  Google Scholar 

  20. Burtseva, N. N., Axizov, Yu. M., Itkin, B. Z. & Vanyushin, B. F. Biokhimiya 42, 1690–1696 (1977).

    CAS  Google Scholar 

  21. Lapeyre, J.-N. & Becker, F.F. Biochem. biophys. Res. Commun. 87, 698–705 (1979).

    Article  CAS  Google Scholar 

  22. Cohen, J. C. Cell 19, 653–662 (1980).

    Article  CAS  Google Scholar 

  23. Reilly, J. G., Thomas, C. A. Jr & Sen, A. Biochim. biophys. Acta 697, 53–59 (1982).

    Article  CAS  Google Scholar 

  24. Nakhasi, H. L. et al. J. biol. Chem. 257, 2726–2729 (1982).

    CAS  PubMed  Google Scholar 

  25. Gantt, R., de Oca, F. M. & Evans, V. J. In Vitro 8, 288–294 (1973).

    Article  CAS  Google Scholar 

  26. Singer, J., Stellwagen, R. H., Roberts-Ems, J. & Riggs, A. D. J. biol. Chem. 252, 5509–5513, (1977).

    CAS  PubMed  Google Scholar 

  27. Browne, M. J. & Burdon, R. H. Nucleic Acids Res. 4, 1025–1037 (1977).

    Article  CAS  Google Scholar 

  28. Diala, E. S. & Hoffman, R. M. Biochem. biophys. Res. Commun. 104, 1489–1494 (1982).

    Article  CAS  Google Scholar 

  29. McKeon, C., Ohkubo, H., Pastan, I. & de Crombrugghe, B. Cell 29, 203–210 (1982).

    Article  CAS  Google Scholar 

  30. Kuhlmann, I. & Doerfler, W. Virology 118, 169–180 (1982).

    Article  CAS  Google Scholar 

  31. Mann, M. B. & Smith, H. O. Nucleic Acids Res. 4, 4211–4221 (1977).

    Article  CAS  Google Scholar 

  32. Bird, A. P. & Southern, E. M. J. molec. Biol. 118, 27–47 (1978).

    Article  CAS  Google Scholar 

  33. Van der Ploeg, L. H. T. & Flavell, R. A. Cell 19, 947–958 (1980).

    Article  CAS  Google Scholar 

  34. Hall, R. H. The Modified Nucleosides in Nucleic Acids, 281–294 (Columbia, New York, 1971).

    Google Scholar 

  35. Bird, A. P. J. molec. Biol. 118, 49–60 (1978).

    Article  CAS  Google Scholar 

  36. Pollack, Y., Stein, R., Razin, A. & Cedar, H. Proc. natn. Acad. Sci. U.S.A. 77, 6463–6467 (1980).

    Article  ADS  CAS  Google Scholar 

  37. Wigler, M., Levy, D. & Perucho, M. Cell 24, 33–40 (1981).

    Article  CAS  Google Scholar 

  38. Harland, R. M. Proc. natn. Acad. Sci. U.S.A. 79, 2323–2327 (1982).

    Article  ADS  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  42. Wilson, J. T. et al. Nucleic Acids Res. 5, 563–581 (1978).

    Article  CAS  Google Scholar 

  43. Sugarbaker, P. H., Macdonald, J. S. & Gunderson, L. L. in Cancer: Principles and Practice of Oncology (eds De Vita, V. T. Jr, Hellman, S.&Rosenberg, S. A.) 643–723 (Lippincott, Philadelphia, 1982).

    Google Scholar 

  44. Moore, D. D., Conkling, M. A. & Goodman, H. M. Cell 29, 285–286 (1982).

    Article  CAS  Google Scholar 

  45. Waalwijk, C. & Flavell, R. A. Nucleic Acids Res. 5, 3231–3236 (1978).

    Article  CAS  Google Scholar 

  46. Sneider, T. W. Nucleic Acids Res. 8, 3829–3840 (1980).

    Article  CAS  Google Scholar 

  47. Van der Ploeg, L. H. T., Groffen, J. & Flavell, R. A. Nucleic Acids Res. 8, 4563–4574 (1980).

    Article  CAS  Google Scholar 

  48. Stein, R., Gruenbaum, Y., Pollack, Y., Razin, A. & Cedar, H. Proc. natn. Acad. Sci. U.S.A. 79, 61–65 (1982).

    Article  ADS  CAS  Google Scholar 

  49. Owens, A. H., Coffey, D. S. & Baylin, S. B. Tumor Cell Heterogeneity: Origins and Implications (Academic, New York, 1982).

    Google Scholar 

  50. McKusick, V. A. Cytogenet. Cell Genet. 32, 1–343 (1982).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  52. Brunk, C. F., Jones, K. C. & James, T. W. Analyt. Biochem. 92, 497–500 (1979).

    Article  CAS  Google Scholar 

  53. Colman, A., Byers, M.J., Primose, S.B. & Lyons, A. Eur. J. Biochem. 91, 303–310 (1978).

    Article  CAS  Google Scholar 

  54. Birnboim, H. C. & Dolly, J. Nucleic Acids Res. 7, 1513–1523 (1979).

    Article  CAS  Google Scholar 

  55. Feinberg, A. P. & Vogelstein, B. Analyt. Biochem. (submitted).

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

    Article  CAS  Google Scholar 

  57. Laskey, R. A. & Mills, A. D. FEBS Lett. 82, 314–316 (1977).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cell Structure and Function Laboratory, The Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA

    Andrew P. Feinberg & Bert Vogelstein

Authors
  1. Andrew P. Feinberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bert Vogelstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Feinberg, A., Vogelstein, B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301, 89–92 (1983). https://doi.org/10.1038/301089a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/301089a0

This article is cited by

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.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing