Gene silencing associated with aberrant DNA methylation of promoter CpG islands is one mechanism through which several genes may be inactivated in human
cancers.
Cyclin D2, a member of the D-type
cyclins, implicated in cell cycle regulation, differentiation and malignant transformation, is inactivated due to aberrant DNA methylation in several human
cancers. In the present study, we examined the promoter methylation status and expression of
Cyclin D2 in human
epithelial ovarian cancer, and then determined the relationship between methylation status and various clinicopathological variables. Twelve
ovarian cancer cell lines and 71 surgical specimens were examined by methylation-specific polymerase chain reaction and quantitative reverse transcription-polymerase chain reaction to evaluate the methylation status and expression of the
Cyclin D2 gene. The relationship between methylation status and various clinicopathological variables was evaluated using statistical analysis. Aberrant methylation of
Cyclin D2 was present in five of 12
ovarian cancer cell lines and 16 of 71 primary
ovarian cancer tissues. In five cell lines with methylation, expression of the
Cyclin D2 gene tended to be lower than in cell lines without methylation. In
ovarian cancer tissues, methylation bands were detected in 16 of 71 cases. The methylation status of
Cyclin D2 was associated with advanced stage and a
residual tumor size (>2 cm) (P = 0.027 and P = 0.031, respectively). Based on univariate analysis, patients with aberrant methylation of the
Cyclin D2 promoter had a significantly worse chance of disease-free survival than those without methylation (P = 0.021). Our results suggest that aberrant promoter methylation of the
Cyclin D2 gene is significantly associated with patient prognosis in
epithelial ovarian cancer.