Skip to main content

Advertisement

SpringerLink
Log in

Methylation in the p53 promoter in epithelial ovarian cancer

  • Brief Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Objective

Ovarian cancer is a leading cause of death from gynecologic tumors, however, the molecular and especially epigenetic events underlying this transformation are poorly understood. Promoter methylation status of tumor suppressor genes may be associated with transcriptional silencing and tumor progression. It has been shown that methylation of CpG dinucleotides located in the promoter region of p53 is associated with low expression levels of this gene. The aim of this study was to investigate promoter methylation of p53 gene in ovarian cancer by comparison with normal ovarian tissue.

Methods

To search for promoter methylation of p53 gene we used methylation-specific PCR (MSP) to compare the methylation status of 66 tissue samples of ovarian cancer with 37 control samples.

Results

In our study methylation specific PCR revealed p53 promoter methylation in 34 of 66 (51.5 %) of specimens with ovarian cancer.

Conclusion

These results indicate that methylation in p53 promoter region may play an important role in carcinogenesis of ovarian cancer and could potentially be used in screening of ovarian cancer, and may have implications for future chemotherapy based on epigenetic changes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Beth YK (2009) Patients at high risk for ovarian cancer should undergo routine screening. Clin Ovarian Cancer 2:83–89

    Article  Google Scholar 

  2. Jones PA, Baylin SB (2007) The epigenomics of cancer. Cell 128(4):683–692

    Article  PubMed  CAS  Google Scholar 

  3. Chan KY, Ozçelik H, Cheung AN, Ngan HY, Khoo US (2002) Epigenetic factors controlling the BRCA1 and BRCA2 genes in sporadic ovarian cancer. Cancer Res 62(14):4151–4156

    PubMed  CAS  Google Scholar 

  4. Yoon JH, Dammann R, Pfeifer GP (2001) Hypermethylation of the CpG island of the RASSF1A gene in ovarian and renal cell carcinomas. Int J Cancer 94(2):212–217

    Article  PubMed  CAS  Google Scholar 

  5. Gras E, Catasus L, Argüelles R, Moreno-Bueno G, Palacios J, Gamallo C, Matias-Guiu X, Prat J (2001) Microsatellite instability, MLH-1 promoter hypermethylation, and frameshift mutations at coding mononucleotide repeat microsatellites in ovarian tumors. Cancer 92(11):2829–2836

    Article  PubMed  CAS  Google Scholar 

  6. Feng W, Marquez RT, Lu Z, Liu J, Lu KH, Issa JP, Fishman DM, Yu Y, Bast RC Jr (2008) Imprinted tumor suppressor genes ARHI and PEG3 are the most frequently down-regulated in human ovarian cancers by loss of heterozygosity and promoter methylation. Cancer 112(7):1489–1502

    Article  PubMed  CAS  Google Scholar 

  7. Mei FC, Young TW, Liu J, Cheng X (2006) RAS-mediated epigenetic inactivation of OPCML in oncogenic transformation of human ovarian surface epithelial cells. FASEB J 20(3):497–499

    PubMed  CAS  Google Scholar 

  8. Lane DP (1994) p53 and human cancers. Br Med Bull 50:582–599

    PubMed  CAS  Google Scholar 

  9. Tuck SP, Crawford L (1989) Characterization of the human p53 gene promoter. Mol Cell Biol 9(5):2163–2172

    PubMed  CAS  Google Scholar 

  10. Marks JR, Davidoff AM, Kerns BJ et al (1991) Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res 51(11):2979–2984

    PubMed  CAS  Google Scholar 

  11. Kang JH, Kim SJ, Noh DY, Park IA, Choe KJ, Yoo OJ, Kang HS (2001) Methylation in the p53 promoter is a supplementary route to breast carcinogenesis: correlation between CpG methylation in the p53 promoter and the mutation of the p53 gene in the progression from ductal carcinoma in situ to invasive ductal carcinoma. Lab Invest 81(4):573–579

    Article  PubMed  CAS  Google Scholar 

  12. Amatya VJ, Naumann U, Weller M, Ohgaki H (2005) TP53 promoter methylation in human gliomas. Acta Neuropathol 110(2):178–184

    Article  PubMed  CAS  Google Scholar 

  13. Agirre X, Vizmanos JL, Calasanz MJ, García-Delgado M, Larráyoz MJ, Novo FJ (2003) Methylation of CpG dinucleotides and/or CCWGG motifs at the promoter of TP53 correlates with decreased gene expression in a subset of acute lymphoblastic leukemia patients. Oncogene 22(7):1070–1072

    Article  PubMed  CAS  Google Scholar 

  14. Pogribny IP, James SJ (2002) Reduction of p53 gene expression in human primary hepatocellular carcinoma is associated with promoter region methylation without coding region mutation. Cancer Lett 176(2):169–174

    Article  PubMed  CAS  Google Scholar 

  15. Tavassoli FA, Devilee P (eds) (2003) World Health Organization classification of tumors: pathology and genetics of tumors of the breast and female genital organs. IARC Press, Lyon, pp 113–202

    Google Scholar 

  16. Herman JG, Graff JR, Myöhänen S, Nelkin BD, Baylin SB (1996) Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA 93(18):9821–9826

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by research project MZO 00179906 and by Grant SVV-2011-262902.

Conflict of interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

  1. Institute of Clinical Biochemistry and Diagnostics, Medical Faculty of Charles University and Faculty Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic

    Marcela Chmelarova, M. Beranek & V. Palicka

  2. Department of Obstetrics and Gynecology, Medical Faculty of Charles University and Faculty Hospital Hradec Kralove, Hradec Kralove, Czech Republic

    E. Krepinska & J. Spacek

  3. The Fingerland Department of Pathology, Medical Faculty of Charles University and Faculty Hospital Hradec Kralove, Hradec Kralove, Czech Republic

    J. Laco

Authors
  1. Marcela Chmelarova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Krepinska
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Spacek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Laco
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Beranek
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. Palicka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marcela Chmelarova.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chmelarova, M., Krepinska, E., Spacek, J. et al. Methylation in the p53 promoter in epithelial ovarian cancer. Clin Transl Oncol 15, 160–163 (2013). https://doi.org/10.1007/s12094-012-0894-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-012-0894-z

Keywords

Search

Navigation