Aberrant promoter methylation and silencing of RASSF2A gene in cervical cancer

AimRas association domain family (RASSF)2A as a negative effector of Ras protein is inactivated by promoter hypermethylation in many cancers. This study evaluated the methylation status of RASSF2A in cervical cancer (CC) and its correlation with clinicopathological characteristics. MethodsMethylation-specific polymerase chain reaction and reverse transcriptase polymerase chain reaction were utilized to analyze the methylation status and RASSF2AmRNA expression in four CC cell lines and tissue samples from 25 normal controls and 46 CC patients. The CC cell lines also were treated with the methyltransferase inhibitor 5-aza-2-deoxycytidine (5-aza-dC). ResultsExpression of RASSF2A was downregulated in all cell lines and CC tissue samples. Hypermethylation of RASSF2A was detected in all cell lines and 26 of 46 (56.5%) CC samples. No methylation of RASSF2A was found in the normal cervical tissues. A decreased level (P<0.05) of RASSF2A expression was observed among RASSF2A-methylated CC cases (0.10020.0377, mean +/- standard deviation) compared to unmethylated cases (0.2882 +/- 0.0642, mean +/- standard deviation). After treatment with 5-aza-dC, loss of RASSF2A expression was restored in four CC cell lines. RASSF2A methylation was significantly different in patients with or without lymph node metastasis (90% vs 47.2%, respectively; P<0.05). ConclusionPromoter hypermethylation of RASSF2A is observed in CC, while not in normal cervical tissues. RASSF2A is inactivated in CC by promoter hypermethylation and may play a role in cervical carcinogenesis.