Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Jul 15;89(14):6516–6520. doi: 10.1073/pnas.89.14.6516

An infrequent point mutation of the p53 gene in human nasopharyngeal carcinoma.

Y Sun 1, G Hegamyer 1, Y J Cheng 1, A Hildesheim 1, J Y Chen 1, I H Chen 1, Y Cao 1, K T Yao 1, N H Colburn 1
PMCID: PMC49532  PMID: 1631151

Abstract

Point mutations in the p53 gene have been detected in a variety of human cancers; the mutations are clustered in four "hot-spots" located in the coding region of exons 5, 7, and 8, which coincide with the four most highly conserved regions of the gene. We report the finding of a heterozygous G----C mutation at codon 280 (exon 8), position 2, of the p53 gene in a nasopharyngeal carcinoma (NPC) cell line, originating from Guangdong, a province in the People's Republic of China that leads the world in NPC incidence. A survey of nasopharyngeal tissues and NPC biopsies revealed that 1 out of 12 NPC samples from Hunan, another province in the People's Republic of China with high NPC incidence, had the same heterozygous mutation at codon 280 of p53, and none of 10 biopsies from Taiwan showed a mutation within exons 5-8 of the p53 gene. No other alteration of gene structure, including gross rearrangement or loss of heterozygosity or abnormality of gene expression was detected in NPC cell lines or NPC biopsies. We conclude from this study that mutational or other alterations of the p53 gene are not common in nasopharyngeal carcinogenesis and that a codon-280 mutation of p53 may be involved in less than 10% of NPC cases. This result contrasts with the relatively high frequency of p53 mutations associated with several other human carcinomas and suggests the importance of other genes in NPC genesis.

Full text

PDF
6516

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Armstrong R. W., Armstrong M. J., Yu M. C., Henderson B. E. Salted fish and inhalants as risk factors for nasopharyngeal carcinoma in Malaysian Chinese. Cancer Res. 1983 Jun;43(6):2967–2970. [PubMed] [Google Scholar]
  2. Bartek J., Iggo R., Gannon J., Lane D. P. Genetic and immunochemical analysis of mutant p53 in human breast cancer cell lines. Oncogene. 1990 Jun;5(6):893–899. [PubMed] [Google Scholar]
  3. Bischoff J. R., Friedman P. N., Marshak D. R., Prives C., Beach D. Human p53 is phosphorylated by p60-cdc2 and cyclin B-cdc2. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4766–4770. doi: 10.1073/pnas.87.12.4766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bressac B., Kew M., Wands J., Ozturk M. Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature. 1991 Apr 4;350(6317):429–431. doi: 10.1038/350429a0. [DOI] [PubMed] [Google Scholar]
  5. Buchman V. L., Chumakov P. M., Ninkina N. N., Samarina O. P., Georgiev G. P. A variation in the structure of the protein-coding region of the human p53 gene. Gene. 1988 Oct 30;70(2):245–252. doi: 10.1016/0378-1119(88)90196-5. [DOI] [PubMed] [Google Scholar]
  6. Cao Y., Sun Y., Poirier S., Winterstein D., Hegamyer G., Seed J., Malin S., Colburn N. H. Isolation and partial characterization of a transformation-associated sequence from human nasopharyngeal carcinoma. Mol Carcinog. 1991;4(4):297–307. doi: 10.1002/mc.2940040408. [DOI] [PubMed] [Google Scholar]
  7. Chen P. L., Chen Y. M., Bookstein R., Lee W. H. Genetic mechanisms of tumor suppression by the human p53 gene. Science. 1990 Dec 14;250(4987):1576–1580. doi: 10.1126/science.2274789. [DOI] [PubMed] [Google Scholar]
  8. Cheng J., Haas M. Frequent mutations in the p53 tumor suppressor gene in human leukemia T-cell lines. Mol Cell Biol. 1990 Oct;10(10):5502–5509. doi: 10.1128/mcb.10.10.5502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chiba I., Takahashi T., Nau M. M., D'Amico D., Curiel D. T., Mitsudomi T., Buchhagen D. L., Carbone D., Piantadosi S., Koga H. Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung Cancer Study Group. Oncogene. 1990 Oct;5(10):1603–1610. [PubMed] [Google Scholar]
  10. Emini E. A., Hughes J. V., Perlow D. S., Boger J. Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide. J Virol. 1985 Sep;55(3):836–839. doi: 10.1128/jvi.55.3.836-839.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Farrell P. J., Allan G. J., Shanahan F., Vousden K. H., Crook T. p53 is frequently mutated in Burkitt's lymphoma cell lines. EMBO J. 1991 Oct;10(10):2879–2887. doi: 10.1002/j.1460-2075.1991.tb07837.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Finlay C. A., Hinds P. W., Levine A. J. The p53 proto-oncogene can act as a suppressor of transformation. Cell. 1989 Jun 30;57(7):1083–1093. doi: 10.1016/0092-8674(89)90045-7. [DOI] [PubMed] [Google Scholar]
  13. Gaidano G., Ballerini P., Gong J. Z., Inghirami G., Neri A., Newcomb E. W., Magrath I. T., Knowles D. M., Dalla-Favera R. p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5413–5417. doi: 10.1073/pnas.88.12.5413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Garnier J., Osguthorpe D. J., Robson B. Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol. 1978 Mar 25;120(1):97–120. doi: 10.1016/0022-2836(78)90297-8. [DOI] [PubMed] [Google Scholar]
  15. Glaser R., Zhang H. Y., Yao K. T., Zhu H. C., Wang F. X., Li G. Y., Wen D. S., Li Y. P. Two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus that were derived from nasopharyngeal carcinomas. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9524–9528. doi: 10.1073/pnas.86.23.9524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Graham F. L., Smiley J., Russell W. C., Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol. 1977 Jul;36(1):59–74. doi: 10.1099/0022-1317-36-1-59. [DOI] [PubMed] [Google Scholar]
  17. Herskowitz I. Functional inactivation of genes by dominant negative mutations. Nature. 1987 Sep 17;329(6136):219–222. doi: 10.1038/329219a0. [DOI] [PubMed] [Google Scholar]
  18. Hollstein M. C., Metcalf R. A., Welsh J. A., Montesano R., Harris C. C. Frequent mutation of the p53 gene in human esophageal cancer. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9958–9961. doi: 10.1073/pnas.87.24.9958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  20. Hsu I. C., Metcalf R. A., Sun T., Welsh J. A., Wang N. J., Harris C. C. Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature. 1991 Apr 4;350(6317):427–428. doi: 10.1038/350427a0. [DOI] [PubMed] [Google Scholar]
  21. Jones P. A., Buckley J. D., Henderson B. E., Ross R. K., Pike M. C. From gene to carcinogen: a rapidly evolving field in molecular epidemiology. Cancer Res. 1991 Jul 1;51(13):3617–3620. [PubMed] [Google Scholar]
  22. Kraiss S., Quaiser A., Oren M., Montenarh M. Oligomerization of oncoprotein p53. J Virol. 1988 Dec;62(12):4737–4744. doi: 10.1128/jvi.62.12.4737-4744.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lerman M. I., Sakai A., Yao K. T., Colburn N. H. DNA sequences in human nasopharyngeal carcinoma cells that specify susceptibility to tumor promoter-induced neoplastic transformation. Carcinogenesis. 1987 Jan;8(1):121–127. doi: 10.1093/carcin/8.1.121. [DOI] [PubMed] [Google Scholar]
  24. Linzer D. I., Levine A. J. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell. 1979 May;17(1):43–52. doi: 10.1016/0092-8674(79)90293-9. [DOI] [PubMed] [Google Scholar]
  25. Marshall C. J. Tumor suppressor genes. Cell. 1991 Jan 25;64(2):313–326. doi: 10.1016/0092-8674(91)90641-b. [DOI] [PubMed] [Google Scholar]
  26. Mazars R., Pujol P., Maudelonde T., Jeanteur P., Theillet C. p53 mutations in ovarian cancer: a late event? Oncogene. 1991 Sep;6(9):1685–1690. [PubMed] [Google Scholar]
  27. Milner J., Medcalf E. A. Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation. Cell. 1991 May 31;65(5):765–774. doi: 10.1016/0092-8674(91)90384-b. [DOI] [PubMed] [Google Scholar]
  28. Nigro J. M., Baker S. J., Preisinger A. C., Jessup J. M., Hostetter R., Cleary K., Bigner S. H., Davidson N., Baylin S., Devilee P. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989 Dec 7;342(6250):705–708. doi: 10.1038/342705a0. [DOI] [PubMed] [Google Scholar]
  29. Oka K., Ishikawa J., Bruner J. M., Takahashi R., Saya H. Detection of loss of heterozygosity in the p53 gene in renal cell carcinoma and bladder cancer using the polymerase chain reaction. Mol Carcinog. 1991;4(1):10–13. doi: 10.1002/mc.2940040104. [DOI] [PubMed] [Google Scholar]
  30. Osborne R. J., Merlo G. R., Mitsudomi T., Venesio T., Liscia D. S., Cappa A. P., Chiba I., Takahashi T., Nau M. M., Callahan R. Mutations in the p53 gene in primary human breast cancers. Cancer Res. 1991 Nov 15;51(22):6194–6198. [PubMed] [Google Scholar]
  31. Rhim J. S., Jay G., Arnstein P., Price F. M., Sanford K. K., Aaronson S. A. Neoplastic transformation of human epidermal keratinocytes by AD12-SV40 and Kirsten sarcoma viruses. Science. 1985 Mar 8;227(4691):1250–1252. doi: 10.1126/science.2579430. [DOI] [PubMed] [Google Scholar]
  32. Sarnow P., Ho Y. S., Williams J., Levine A. J. Adenovirus E1b-58kd tumor antigen and SV40 large tumor antigen are physically associated with the same 54 kd cellular protein in transformed cells. Cell. 1982 Feb;28(2):387–394. doi: 10.1016/0092-8674(82)90356-7. [DOI] [PubMed] [Google Scholar]
  33. Sizhong Z., Xiukung G., Yi Z. Cytogenetic studies on an epithelial cell line derived from poorly differentiated nasopharyngeal carcinoma. Int J Cancer. 1983 May 15;31(5):587–590. doi: 10.1002/ijc.2910310509. [DOI] [PubMed] [Google Scholar]
  34. Sun Y., Hegamyer G., Colburn N. H. A simple method using PCR for direct sequencing of genomic DNA from frozen tumor tissue embedded in optimal cutting temperature compound. Biotechniques. 1992 May;12(5):639–640. [PubMed] [Google Scholar]
  35. Van Roy F., Fransen L., Fiers W. Protein kinase activities in immune complexes of simian virus 40 large T-antigen and transformation-associated cellular p53 protein. Mol Cell Biol. 1984 Feb;4(2):232–239. doi: 10.1128/mcb.4.2.232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Werness B. A., Levine A. J., Howley P. M. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science. 1990 Apr 6;248(4951):76–79. doi: 10.1126/science.2157286. [DOI] [PubMed] [Google Scholar]
  37. Wright P. A., Lemoine N. R., Goretzki P. E., Wyllie F. S., Bond J., Hughes C., Röher H. D., Williams E. D., Wynford-Thomas D. Mutation of the p53 gene in a differentiated human thyroid carcinoma cell line, but not in primary thyroid tumours. Oncogene. 1991 Sep;6(9):1693–1697. [PubMed] [Google Scholar]
  38. Yao K. T., Zhang H. Y., Zhu H. C., Wang F. X., Li G. Y., Wen D. S., Li Y. P., Tsai C. H., Glaser R. Establishment and characterization of two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus and derived from nasopharyngeal carcinomas. Int J Cancer. 1990 Jan 15;45(1):83–89. doi: 10.1002/ijc.2910450116. [DOI] [PubMed] [Google Scholar]
  39. Yu M. C., Mo C. C., Chong W. X., Yeh F. S., Henderson B. E. Preserved foods and nasopharyngeal carcinoma: a case-control study in Guangxi, China. Cancer Res. 1988 Apr 1;48(7):1954–1959. [PubMed] [Google Scholar]
  40. Zakut-Houri R., Bienz-Tadmor B., Givol D., Oren M. Human p53 cellular tumor antigen: cDNA sequence and expression in COS cells. EMBO J. 1985 May;4(5):1251–1255. doi: 10.1002/j.1460-2075.1985.tb03768.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Zeng Y., Zhong J. M., Mo Y. K., Miao X. C. Epstein-Barr virus early antigen induction in Raji cells by Chinese medicinal herbs. Intervirology. 1983;19(4):201–204. doi: 10.1159/000149361. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES