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Assessment of DNA Methylation in p15, p16 and E-Cadherin Genes as a Screening Tool for Early Carcinoma Cervix

  • M. BanerjeeEmail author
  • K. Kulhari
  • T. K. Saha
Original Research Article
  • 5 Downloads

Abstract

Cancer cervix is diagnosed late in women due to anatomical inaccessibility of the area. Hence, a robust screening strategy will help detect carcinoma cervix early which will significantly decrease the mortality and morbidity due to this disease. We evaluated DNA methylation of three tumour suppressor genes p15, p16 and E-Cadherin on cervical smears to assess DNA methylation as a screening tool for detection of early cervical cancer in comparison to PAP smears. DNA was extracted from cervical smears of 20 cases and 30 controls. The DNA was bisulphite modified. Methylation specific PCR (MSP) was performed to assess the methylation status of the promoter region of each of the genes. MSP results were compared with PAP smears to assess the utility of DNA methylation of these genes in screening for cervical cancer. DNA methylation was detected in 55% subjects in p15 gene, 45% in p16 gene and 40% in E-Cadherin gene. This was statistically significant when compared to the controls. DNA methylation of E-Cadherin, and p15 genes as a panel has a sensitivity and specificity of 80% and 90% respectively, which is better than the sensitivity of PAP smear for detection of early cancer cervix. Increased DNA methylation is seen in p15, p16 and E-Cadherin genes in early cancer cervix. p15 and E-Cadherin in combination can be used as a screening tool for detection of early cancer cervix.

Keywords

Methylation specific PCR Methylation Tumour suppressor Dysplasia PAP smear 

Notes

Acknowledgements

The article is based on grants from Defence Research Development Organisation vide Armed Forces Medical Research Committee AFMRC 3857/2008.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed Consent

The research was performed on human cervical smear samples after taking due consent from each patient and control after informing them about the study.

References

  1. 1.
    Zahava S, Howard C. DNA methylation: a molecular lock. Curr Biol. 1997;7:305–7.CrossRefGoogle Scholar
  2. 2.
    Momparler RL, Bovenzi V. DNA methylation and cancer. J Cell Physiol. 2000;183:145–54.CrossRefGoogle Scholar
  3. 3.
    Kumar V, Abbas AK, Fausto N, Aster JC. Neoplasia. In: Kumar V, Abbas AK, Fausto N, Aster JC, editors. Pathologic basis of disease. 9th ed. Philadelphia: Elsevier; 2010. pp. 265–340.Google Scholar
  4. 4.
    Rocco JW, Sidransky D. p16 (MTS-1/CDKN2/INK4a) in cancer progression. Exp Cell Res. 2001;264:42–55.CrossRefGoogle Scholar
  5. 5.
    Kim DH, Nelson HH, Wiencke JK, Shichun Z, Christiani DC, Wain JC, et al. p16 (INK4a) and histology-specific methylation of CpG islands by exposure to tobacco smoke in non-small cell lung cancer. Cancer Res. 2001;61:3419–24.Google Scholar
  6. 6.
    Bai M, Vlachonikolis J, Agnantis NJ. Low expression of p27 protein combined with altered p53 and RB/p16 expression status is associated with increased expression of cyclin A and cyclin B1 in diffuse large cell lymphomas. Mod Pathol. 2001;14:1105–13.CrossRefGoogle Scholar
  7. 7.
    Attaleb M, El Hamadani W, Khyatti M, Benbacer L, BenchekrounN Benider A, et al. Status of p16(INK4a) and E-cadherin gene promoter methylation in Moroccan patients with cervical carcinoma. Oncol Res. 2009;18:185–92.CrossRefGoogle Scholar
  8. 8.
    Ren CC, Miao XH, Yang B, Zhao L, Sun R, Song WQ. Methylation status of the fragile histidine triad and E-cadherin genes in plasma of cervical cancer patients. Int J Gynecol Cancer. 2006;16:1862–7.CrossRefGoogle Scholar
  9. 9.
    Nayera HELS, Ghada IM. p15 (INK4B) and E-Cadherin CpG Island Methylation is frequent in Egyptian Acute Myeloid Leukemia. J Egypt Natl Cancer Inst. 2006;18:227–32.Google Scholar
  10. 10.
    Kim JH, Choi YD, Lee JS, Lee JH, Nam JH, Choi C. Assessment of DNA methylation for the detection of cervical neoplasia in liquid-based cytology specimens. Gynaecol Oncol. 2010;116:99–104.CrossRefGoogle Scholar
  11. 11.
    Wen HL, Shan PH, Hung LY, Min SK, Ju CH, Loung HJ, et al. P16 Methylation is an early event in cervical carcinogenesis. Int J Gynecol Cancer. 2011;21:452–6.CrossRefGoogle Scholar
  12. 12.
    Xu J, Wang HL, Lu GC, Wang ZJ, Lin X, Zhou HW. Clinical significance of detection of tumor suppressor genes aberrant methylation in cervical carcinoma tissue. Zhonghua Fu Chan KeZa Zhi. 2007;4296:394–7.Google Scholar
  13. 13.
    Tien HF, Tang JH, Tsay W, Liu MC, Lee FY, Wang CH, et al. Methylation of the p15 gene in Myelodysplastic syndrome: it can be detected early in at diagnosis or during disease progression and is highly associated with leukaemic transformation. Br J Haematol. 2001;112:148–54.CrossRefGoogle Scholar
  14. 14.
    Howell PM, Liu Z, Khong HT. Demethylating agents in the treatment of cancer. Pharmaceuticals. 2010;3:2022–44.CrossRefGoogle Scholar
  15. 15.
    Pacheco BS, Becerril CT, Cardenas EP, Chayeb LT, Mariscal I, Chavez A, et al. Reactivation of tumor suppressor genes by the cardiovascular drugs hydralazine and procainamide and their potential use in cancer therapy. Clin Cancer Res. 2003;9:1596–2004.Google Scholar

Copyright information

© Association of Clinical Biochemists of India 2019

Authors and Affiliations

  1. 1.All India Institute of Medical SciencesJodhpurIndia
  2. 2.Command Hospital ChandigarhChandimandirIndia
  3. 3.Department of BiochemistryAl Falah School of Medical Science and Research CentreFaridabadIndia

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