Assessment of DNA Methylation in p15, p16 and E-Cadherin Genes as a Screening Tool for Early Carcinoma Cervix
- 5 Downloads
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.
KeywordsMethylation specific PCR Methylation Tumour suppressor Dysplasia PAP smear
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.
The research was performed on human cervical smear samples after taking due consent from each patient and control after informing them about the study.
- 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
- 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
- 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
- 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
- 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