Methylation status of the gene promoter of cyclin-dependent kinase inhibitor 2A (CDKN2A) in ovarian cancer

Abstract

Objective. This study investigated the methylation status of the promoter of the tumor suppressor gene cyclin-dependent kinase inhibitor 2A (CDKN2A) in ovarian cancer. Design and methods. CDKN2A methylation was quantified by real-time PCR in ovarian biopsies of 52 patients with ovarian cancer, 43 patients with benign ovarian tumors and 40 patients with benign uterine pathology and healthy ovaries. Results. CDKN2A methylation was detected in the three groups. The methylation level was higher in the cancer patients than in the other two groups (p = 0.0003) but was not different between benign tumors and healthy ovarian tissue (p > 0.05). Using a cutoff threshold based on receiver-operating characteristic analysis, 21 patients with ovarian cancer and three patients with benign tumors were considered positive for CDKN2A methylation while all patients with healthy ovaries were considered negative. At the chosen cutoff, the diagnostic sensitivity was 40.4% and specificity 96.4%. CDKN2A methylation level and frequency were associated with high grade tumors (p = 0.0001 and p = 0.0005) but were not associated with disease stage or serum CA125 levels. However, it should be noted that most patients (92.3%) presented with advanced stage 3 or 4 disease. Conclusion. CDKN2A promoter methylation is common in ovarian cancer. Quantification of CDKN2A methylation may be useful in distinguishing malignant from benign ovarian tumors or healthy ovarian tissue.

Key Words::

• Cyclin-dependent kinase inhibitor 2
• DNA methylation
• gene silencing
• DNA testing
• ovarian cancer
• real-time PCR
• tumor suppressor genes

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper. No funding was received.