Alteration of p53 gene in ovarian carcinoma: clinicopathological correlation and prognostic significance (original) (raw)

Abstract

Inactivation of the tumour-suppressor gene p53 has been demonstrated in a variety of human tumours. We extracted DNA from paraffin-embedded tissues of 67 ovarian carcinoma samples (54 primary tumours, seven metastases and six tumours obtained after chemotherapy), and analysed allelic losses and mutations of the p53 gene using single-strand conformation polymorphism (SSCP) analysis of DNA fragments amplified by a polymerase chain reaction (PCR). Allelic loss was observed in 24 of 32 informative cases. The mutation was detected in 14 of 54 primary ovarian carcinomas: eight serous cystadenocarcinomas (SCA), 42%), five endometrioid adenocarcinomas (EA, 42%) and one mucinous cystadenocarcinoma (14%). The incidence of the alteration was higher in SCA and EA than in other histological types, but the difference was not statistically significant. The incidence of p53 gene abnormalities in ovarian carcinomas tended to be increased in patients with disease advanced (over FIGO stage II). Mutations were found in exons 5 and 7 only and consisted mainly of single nucleotide substitutions [9 or 14 (64%) in exon 7; 4 of 14 (29%) in exon 5]. In 13 of 14 cases, p53 gene mutations occurred concomitantly with losses of the normal allele. The status of the p53 gene in metastases and the tumours obtained after chemotherapy was identical to that in the primary tumours. The presence of p53 gene mutation did not correlate with histological grade, response to primary therapy and survival. These findings suggest that mutational alterations of the p53 gene are involved in the development of a significant proportion of some ovarian carcinomas (SCAs or EAs), especially in advanced stages. However, they may not be a marker predicting the biological behaviour or the outcome of the disease.

1191

Images in this article

Selected References

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

  1. Baker S. J., Markowitz S., Fearon E. R., Willson J. K., Vogelstein B. Suppression of human colorectal carcinoma cell growth by wild-type p53. Science. 1990 Aug 24;249(4971):912–915. doi: 10.1126/science.2144057. [DOI] [PubMed] [Google Scholar]
  2. Baker S. J., Preisinger A. C., Jessup J. M., Paraskeva C., Markowitz S., Willson J. K., Hamilton S., Vogelstein B. p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res. 1990 Dec 1;50(23):7717–7722. [PubMed] [Google Scholar]
  3. 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]
  4. Beck S., O'Keeffe T., Coull J. M., Köster H. Chemiluminescent detection of DNA: application for DNA sequencing and hybridization. Nucleic Acids Res. 1989 Jul 11;17(13):5115–5123. doi: 10.1093/nar/17.13.5115. [DOI] [PMC free article] [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. Caron de Fromentel C., Soussi T. TP53 tumor suppressor gene: a model for investigating human mutagenesis. Genes Chromosomes Cancer. 1992 Jan;4(1):1–15. doi: 10.1002/gcc.2870040102. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Creasey A., D'Angio L., Jr, Dunne T. S., Kissinger C., O'Keeffe T., Perry-O'Keefe H., Moran L. S., Roskey M., Schildkraut I., Sears L. E. Application of a novel chemiluminescence-based DNA detection method to single-vector and multiplex DNA sequencing. Biotechniques. 1991 Jul;11(1):102-4, 106, 108-9. [PubMed] [Google Scholar]
  9. D'Amico D., Carbone D., Mitsudomi T., Nau M., Fedorko J., Russell E., Johnson B., Buchhagen D., Bodner S., Phelps R. High frequency of somatically acquired p53 mutations in small-cell lung cancer cell lines and tumors. Oncogene. 1992 Feb;7(2):339–346. [PubMed] [Google Scholar]
  10. Eccles D. M., Cranston G., Steel C. M., Nakamura Y., Leonard R. C. Allele losses on chromosome 17 in human epithelial ovarian carcinoma. Oncogene. 1990 Oct;5(10):1599–1601. [PubMed] [Google Scholar]
  11. Eliyahu D., Michalovitz D., Eliyahu S., Pinhasi-Kimhi O., Oren M. Wild-type p53 can inhibit oncogene-mediated focus formation. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8763–8767. doi: 10.1073/pnas.86.22.8763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Filmus J. E., Buick R. N. Stability of c-K-ras amplification during progression in a patient with adenocarcinoma of the ovary. Cancer Res. 1985 Sep;45(9):4468–4472. [PubMed] [Google Scholar]
  13. 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]
  14. Fujimori M., Tokino T., Hino O., Kitagawa T., Imamura T., Okamoto E., Mitsunobu M., Ishikawa T., Nakagama H., Harada H. Allelotype study of primary hepatocellular carcinoma. Cancer Res. 1991 Jan 1;51(1):89–93. [PubMed] [Google Scholar]
  15. Harris C. C. Interindividual variation among humans in carcinogen metabolism, DNA adduct formation and DNA repair. Carcinogenesis. 1989 Sep;10(9):1563–1566. doi: 10.1093/carcin/10.9.1563. [DOI] [PubMed] [Google Scholar]
  16. Hayashi K. PCR-SSCP: a simple and sensitive method for detection of mutations in the genomic DNA. PCR Methods Appl. 1991 Aug;1(1):34–38. doi: 10.1101/gr.1.1.34. [DOI] [PubMed] [Google Scholar]
  17. Hayashi K., Yandell D. W. How sensitive is PCR-SSCP? Hum Mutat. 1993;2(5):338–346. doi: 10.1002/humu.1380020503. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Hunter T. Cooperation between oncogenes. Cell. 1991 Jan 25;64(2):249–270. doi: 10.1016/0092-8674(91)90637-e. [DOI] [PubMed] [Google Scholar]
  20. Lee J. H., Kavanagh J. J., Wildrick D. M., Wharton J. T., Blick M. Frequent loss of heterozygosity on chromosomes 6q, 11, and 17 in human ovarian carcinomas. Cancer Res. 1990 May 1;50(9):2724–2728. [PubMed] [Google Scholar]
  21. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep. 1966 Mar;50(3):163–170. [PubMed] [Google Scholar]
  22. Marks J. R., Davidoff A. M., Kerns B. J., Humphrey P. A., Pence J. C., Dodge R. K., Clarke-Pearson D. L., Iglehart J. D., Bast R. C., Jr, Berchuck A. Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res. 1991 Jun 1;51(11):2979–2984. [PubMed] [Google Scholar]
  23. Masharani U., Wolf D., Frossard P. M. BanII and ScaI RFLPs at the human p53 gene locus. Nucleic Acids Res. 1988 Aug 11;16(15):7757–7757. doi: 10.1093/nar/16.15.7757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mashiyama S., Murakami Y., Yoshimoto T., Sekiya T., Hayashi K. Detection of p53 gene mutations in human brain tumors by single-strand conformation polymorphism analysis of polymerase chain reaction products. Oncogene. 1991 Aug;6(8):1313–1318. [PubMed] [Google Scholar]
  25. 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]
  26. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Okamoto A., Sameshima Y., Yokoyama S., Terashima Y., Sugimura T., Terada M., Yokota J. Frequent allelic losses and mutations of the p53 gene in human ovarian cancer. Cancer Res. 1991 Oct 1;51(19):5171–5176. [PubMed] [Google Scholar]
  29. Orita M., Suzuki Y., Sekiya T., Hayashi K. Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics. 1989 Nov;5(4):874–879. doi: 10.1016/0888-7543(89)90129-8. [DOI] [PubMed] [Google Scholar]
  30. Prosser J., Thompson A. M., Cranston G., Evans H. J. Evidence that p53 behaves as a tumour suppressor gene in sporadic breast tumours. Oncogene. 1990 Oct;5(10):1573–1579. [PubMed] [Google Scholar]
  31. Rodrigues N. R., Rowan A., Smith M. E., Kerr I. B., Bodmer W. F., Gannon J. V., Lane D. P. p53 mutations in colorectal cancer. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7555–7559. doi: 10.1073/pnas.87.19.7555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Slagle B. L., Zhou Y. Z., Butel J. S. Hepatitis B virus integration event in human chromosome 17p near the p53 gene identifies the region of the chromosome commonly deleted in virus-positive hepatocellular carcinomas. Cancer Res. 1991 Jan 1;51(1):49–54. [PubMed] [Google Scholar]
  33. Slamon D. J., Godolphin W., Jones L. A., Holt J. A., Wong S. G., Keith D. E., Levin W. J., Stuart S. G., Udove J., Ullrich A. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989 May 12;244(4905):707–712. doi: 10.1126/science.2470152. [DOI] [PubMed] [Google Scholar]
  34. Tamura G., Kihana T., Nomura K., Terada M., Sugimura T., Hirohashi S. Detection of frequent p53 gene mutations in primary gastric cancer by cell sorting and polymerase chain reaction single-strand conformation polymorphism analysis. Cancer Res. 1991 Jun 1;51(11):3056–3058. [PubMed] [Google Scholar]
  35. Zhou D. J., Gonzalez-Cadavid N., Ahuja H., Battifora H., Moore G. E., Cline M. J. A unique pattern of proto-oncogene abnormalities in ovarian adenocarcinomas. Cancer. 1988 Oct 15;62(8):1573–1576. doi: 10.1002/1097-0142(19881015)62:8<1573::aid-cncr2820620819>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]