Abstract
HUMAN hepatocellular carcinomas (HCC) from patients in Qidong, an area of high incidence in China, in which both hepatitis B virus and aflatoxin B1 are risk factors1, were analysed for mutations in p53, a putative tumour-suppressor gene. Eight of the 16 HCC had a point mutation at the third base position of codon 249. The G → T transversion in seven HCC DNA samples and the G → C transversion in the other HCC are consistent with mutations caused by aflatoxin B1 in mutagenesis experiments 2,3. No mutations were found in exons 5, 6, 8 or the remainder of exon 7. These results contrast with p53 mutations previously reported in carcinomas and sarcomas of human lung, colon, oesophagus and breast; these are primarily scattered over four of the five evolution-arily conserved domains, which include codon 249 (refs 4–9). We suggest that the mutant p53 protein may be responsible for a selective clonal expansion of hepatocytes during carcinogenesis.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Sun, T., Wu, S., Wu, Y. & Chu, Y. in Diet, Nutrition and Cancer (ed. Hayashi, Y.) 225–235 (Japan Sci. Soc. Press, Tokyo, 1986).
McMahon, G., Davis, E. F., Huber, L. J., Kim, Y. & Wogan, G. N. Proc. natn. Acad. Sci. U.S.A. 87, 1104–1108 (1990).
Sambamurti, K. et al. Genetics 120, 863–873 (1988).
Nigro, J. M. et al. Nature 342, 705–708 (1989).
Takahashi, T. et al. Science 246, 491–494 (1989).
Iggo, R., Gatter, K., Bartek, J., Lane, D. & Harris, A. L. Lancet 335, 675–679 (1990).
Hollstein, M., Metcalf, R. A., Welsh, J., Montesano, R. & Harris, C. C. Proc. natn. Acad. Sci. U.S.A. 87, 9958–9961 (1990).
Mulligan, L. M., Matlashewski, G., Scrable, H. J. & Cavenee, W. K. Proc. natn. Acad. Sci. U.S.A. 87, 5863–5867 (1990).
Bressac, B. et al. Proc. natn. Acad. Sci. U.S.A. 87, 1973–1977 (1990).
Malkin, D. et al. Science 250, 1233–1238 (1990).
Srivastava, S., Zou, Z. Q., Pirollo, K., Battner, W. A. & Chang, E. H. Nature 348, 747–749 (1990).
Soussi, T., Caron de Fromentel, C., Mechali, M., May, P. & Kress, M. Oncogene 1, 71–78 (1987).
Winberg, G. & Hammarskjold, M. L. Nucleic Acids Res. 8, 253–264 (1980).
Bressac, B., Kew, M., Wands, J. & Ozturk, M. Nature 350, 429–431 (1991).
Kumar, R., Sukumar, S. & Barbacid, M. Science 248, 1101–1104 (1990).
Sukumar, S., Carney, W. P. & Barbacid, M. Science 240, 524–526 (1988).
Ganem, D. & Varmus, H. E. A. Rev. Biochem. 56, 651–693 (1987).
Harris, C. C. Cancer Cells 2, 146–148 (1990).
Wogan, G. N. & Gorelick, N. J. Envir. Hlth Perspect. 62, 5–18 (1985).
Wogan, G. N. Envir. Hlth Perspect. 81, 9–17 (1989).
Autrup, H. et al. Chem. biol. Interact. 50, 15–25 (1984).
Lechner, J. F., Cole, K. E., Reddel, R. R., Anderson, L. & Harris, C. C. Cancer Detect. Prev. 14, 239–244 (1989).
Hsu, I. C. et al. Proc. natn. Acad. Sci. U.S.A. 75, 2003–2007 (1978).
Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).
Edmondson, H. A. & Steiner, P. E. Cancer 7, 462–503 (1954).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hsu, I., Metcalf, R., Sun, T. et al. Mutational hot spot in the p53 gene in human hepatocellular carcinomas. Nature 350, 427–428 (1991). https://doi.org/10.1038/350427a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/350427a0