DNA methylation analysis of WIF1 and DKK4 in cervical precancerous lesions and cancer

Abstract

Epigenetic gene silencing by excessive methylation was found in many tumors. Methylation of tumor suppressor genes is often found in cervical cancer, which is an important pathogenetic factor of oncologic process. The objective of this study was to identify gene methylation of WIF1 and DKK4 events and their usefulness in distinguishing cancer and precancerous lesions from normal cervical cells that could eventually be added to standard diagnostic testing for cervical precancer. We examined methylation index of WIF1 and DKK4 genes in the tissue specimen of 42 women: CIN I in 9 cases, CIN II in 11 cases and CIN III in 10 cases, 7 samples included invasive cancer and control group of 5 normal cases. In analysis of methylation level of WIF1 and DKK4 genes aberrant methylation of WIF1 gene was found in women with CIN+ and aberrant methylation of DKK4 gene was found in all women. There was a trend of methylation level increase according to the severith of the precancerous lesions with the maximum mnethylation levels in cases of invasive cervical cancer. Methylation indexes determination in WIF-1 and DKK-4 genes is a perspective method of cervical cancer diagnostics.

Keywords

• cervical intraepithelial neoplasia, cervical cancer, gene silencing, methylation, wif1, dkk4, tumor suppressor genes