P16 Gene Alterations in Human Ovarian Cancers

Abstract

To determine the alterations of tumor suppressor gene p16INK4A in human ovarian cancers to explore the possibilities of identifying potential minimally invasive markers in blood of the patients, which could help in the clinical practice as a diagnostic and prognostic marker. Ovarian cancer tissue and corresponding blood samples were collected from patients (n = 50). The promoter methylation and mutation status of p16 gene in blood and ovarian tissue DNA was then assessed using methylation-specific polymerase chain reaction and denaturing high-performance liquid chromatography along with DNA sequencing method. In addition, the protein expression in ovarian cancer tissue samples was detected by immunostaining method using monoclonal antibodies against p16. Methylation of p16 was observed in 56% (28/50) of the cases. The data showed concordance in promoter methylation status of p16 gene between the tumor tissue and the corresponding blood DNA samples of the patients with ovarian cancer. There was a weak statistical agreement (Kendall tau b = +0.31), and a perfect correspondence was observed in 50% of the cases. The p16 mutations were comparatively low, revealing only 2 variations among the samples analyzed. The percentage of protein expression was inversely correlated with the p16 gene promoter methylation. This study demonstrates that the p16 gene plays a role in the progression of human ovarian cancers and the blood DNA methylation of p16 gene promoter region is a weak predictor of tumor tissue methylation status.