Mutations in the p53 gene occur in diverse human tumour types


THE p53 gene has been a constant source of fascination since its discovery nearly a decade ago1,2. Originally considered to be an oncogene, several convergent lines of research have indicated that the wild-type gene product actually functions as a tumour suppressor gene3–9. For example, expression of the neoplastic phenotype is inhibited, rather than promoted, when rat cells are transfected with the murine wild-type p53 gene together with mutant p53 genes and/or other oncogenes3,4. Moreover, in human tumours, the short arm of chromosome 17 is often deleted (reviewed in ref. 10). In colorectal cancers, the smallest common region of deletion is centred at 17pl3.1 (ref. 9); this region harbours the p53 gene, and in two tumours examined in detail, the remaining (non-deleted) p53 alleles were found to contain mutations9. This result was provocative because allelic deletion coupled with mutation of the remaining allele is a theoretical hallmark of tumour-suppressor genes11. In the present report, we have attempted to determine the generality of this observation; that is, whether tumours with allelic deletions of chromosome 17p contain mutant p53 genes in the allele that is retained. Our results suggest that (1) most tumours with such allelic deletions contain p53 point mutations resulting in amino-acid substitutions, (2) such mutations are not confined to tumours with allelic deletion, but also occur in at least some tumours that have retained both parental 17p alleles, and (3) p53 gene mutations are clustered in four 'hot-spots' which exactly coincide with the four most highly conserved regions of the gene. These results suggest that p53 mutations play a role in the development of many common human malignancies.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Lane, D. P. & Crawford, L. V. Nature 278, 261–263 (1979).

  2. 2

    Linzer, D. I. H. & Levine, A. J. Cell 17, 43–52 (1979).

  3. 3

    Finlay, C. A., Hinds, P. W. & Levine, A. J. Cell 57, 1083–1093 (1989).

  4. 4

    Eliyahu, D. et al. Proc. natn. Acad. Sci. U.S.A. (in the press).

  5. 5

    Sturzbecher, H.-W., Addison, C. & Jenkins, J. R. Molec. cell. Biol. 8, 3740–3747 (1988).

  6. 6

    Munroe, D. G., Rovinski, B., Bernstein, A. & Benchimol, S. Oncogene 2, 621–624 (1988).

  7. 7

    Wolf, D. & Rotter, V. Proc. natn. Acad. Sci. U.S.A. 82, 790–794 (1985).

  8. 8

    Masuda, H., Miller, C., Koeffler, H. P., Battifora, H. & Cline, M. J. Proc. natn. Acad. Sci. U.S.A. 84, 7716–7719 (1987).

  9. 9

    Baker, S. J. et al. Science 244, 217–221 (1989).

  10. 10

    Cavenee, W. K., Hastie, N. D. & Stanbridge, E. J. eds Current Communications in Molecular Biology: Recessive Oncogenes and Tumor Suppression (Cold Spring Harbor Press, New York, 1989).

  11. 11

    Knudson, A. Cancer Res. 45, 1437–1443 (1985).

  12. 12

    Saiki, R. K. et al. Science 239, 487–491 (1988).

  13. 13

    Kondoleon, S. et al. Nucleic Acids Res. 15, 10605 (1987).

  14. 14

    Nakamura, Y. et al. Nucleic Acids Res. 16, 5707 (1988).

  15. 15

    Buchman, V. L. et al. Gene 70, 245–252 (1988).

  16. 16

    Collins, F. S., Ponder, B. A. J., Seizinger, B. R. & Epstein, C. J. Am. J. hum. Genet. 44, 1–5 (1989).

  17. 17

    Finlay, C. A. et al. Molec. cell. Biol. 8, 531–539 (1988).

  18. 18

    Eliyahu, D. et al. Oncogene 3, 313–321 (1988).

  19. 19

    Soussi, T. et al. Oncogene 1, 71–78 (1987).

  20. 20

    Lee, J. H. et al. Proc. Am. Ass. Cancer Res. 30, 442 (1989).

  21. 21

    Atkin, N. B. & Baker, M. C. Cancer Genet. Cytogenet. 37, 229–233 (1989).

  22. 22

    Yano, T. et al. J. natn. Cancer Inst. 181, 518–523 (1989).

  23. 23

    Tsai, Y. C. et al. Cancer Res. (in the press).

  24. 24

    Herskowitz, I. Nature 329, 219–222 (1987).

  25. 25

    Kraiss, S., Quaiser, A., Oren, M. & Montenach, M. J. Virol. 62, 4737–4744 (1988).

  26. 26

    Kern, S. E. et al. J. Am. Med. Ass. 261, 3099–3103 (1989).

  27. 27

    Haymerle, H. et al. Nucleic Acids Res. 14, 8615–8624 (1986).

  28. 28

    Short, J. M., Fernandez, J. M., Sorge, J. A. & Huse, W. D. Nucleic Acids Res. 16, 7583–7600 (1988).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Further reading


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.