Ma L, Guo Q, Ma Y, Liu F R, Shen X Y
Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, China.
Eur J Gynaecol Oncol. 2009;30(4):370-4.
To investigate the frequency of promoter hypermethylation of RASSF1A gene in ovarian cancers and its correlations to gene expression and clinicopathological characters in the Chinese population.
In this study, we detected the frequency of promoter hypermethylation of the RASSF1A gene in 60 patients with primary serous epithelial ovarian carcinomas (SEOCs) using Methylation-Specific PCR (MSP). The gene expression of mRNA and protein was examined by RT-PCR and Western blot.
The frequency of promoter hypermethylation of RASSF1A in Chinese primary SEOCs was 53.3%, whereas promoter hypermethylation was not found in normal ovarian tissues and benign ovarian tissues. The expression of both mRNA and protein of RASSF1A was significantly down-regulated or lost in the methylated group than in nonmethylated group (p < 0.05, respectively). SEOCs with Stage III, IV exhibited a higher frequency of RASSF1A promoter hypermethylation (70.4%, 81.8%) than those with Stage I or Stage II (16.7%, 20.0%, p < 0.05, respectively). Hypermethylation patterns in RASSF1A were more frequently detected in poorly differentiated SEOCs (78.6%) than in moderately differentiated (23.8%) or in well-differetiated SEOCs (27.3%, p < 0.05, respectively).
The high frequency of promoter hypermethylation of RASSF1A contributes to the gene expression in Chinese primary SEOCs. The inactivation of the RASSF1A gene due to hypermethylation in the promoter region might play a critical role in the pathogenesis of ovarian cancers.
探讨中国人群卵巢癌中RASSF1A基因启动子高甲基化的频率及其与基因表达和临床病理特征的相关性。
本研究采用甲基化特异性PCR（MSP）检测60例原发性浆液性上皮性卵巢癌（SEOC）患者中RASSF1A基因启动子高甲基化的频率。通过逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测mRNA和蛋白质的基因表达。
中国原发性SEOC中RASSF1A基因启动子高甲基化的频率为53.3%，而在正常卵巢组织和良性卵巢组织中未发现启动子高甲基化。与未甲基化组相比，甲基化组中RASSF1A的mRNA和蛋白质表达均显著下调或缺失（p均<0.05）。Ⅲ期、Ⅳ期SEOC中RASSF1A启动子高甲基化的频率（分别为70.4%、81.8%）高于Ⅰ期或Ⅱ期（分别为16.7%、20.0%，p均<0.05）。RASSF1A基因的高甲基化模式在低分化SEOC中（78.6%）比中分化（23.8%）或高分化SEOC中（27.3%）更常见（p均<0.05）。
RASSF1A基因启动子高甲基化频率高与中国原发性SEOC中的基因表达有关。启动子区域高甲基化导致的RASSF1A基因失活可能在卵巢癌的发病机制中起关键作用。
