Aberrant Methylation of RASSF2A in Tumors and Plasma of Patients with Epithelial Ovarian Cancer


Objective: The tumor suppressor gene, Ras-association domain family (RASSF)2A, is inactivated bypromoter hypermethylation in many cancers. The current study was performed to evaluate the methylationstatus of RASSF2A in epithelial ovarian cancer (EOC) tissues and plasma, and correlations with gene expressionand clinicopathologic characteristics.
Method: We detected methylation of the RASSF2A gene in tissues andcorresponding plasma samples from 47 EOC patients and 14 patients with benign ovarian tumors and 10 withnormal ovarian tissues. The methylation status was determined by methylation-specific PCR while gene expressionof mRNA was examined by RT-PCR. The EOC cell line, SKOV3, was treated with 5-aza-2’-deoxycytidine (5-azadC).
Results: RASSF2A mRNA expression was significantly low in EOC tissues. The frequency of aberrantmethylation of RASSF2A was 51.1% in EOC tissues and 36.2% in corresponding plasma samples, whereas suchhypermethylation was not detected in the benign ovarial tumors and normal ovarian samples. The expression ofRASSF2A mRNA was significantly down-regulated or lost in the methylated group compared to the unmethylatedgroup (p﹤0.05). After treatment with 5-aza-dC, RASSF2A mRNA expression was significantly restored in theSkov3 cell line.
Conclusion: Epigenetic inactivation of RASSF2A through aberrant promoter methylation mayplay an important role in the pathogenesis of EOC. Methylation of the RASSF2A gene in plasma may be avaluable molecular marker for the early detection of EOC.