Ozdemir Filiz, Altinisik Julide, Karateke Ates, Coksuer Hakan, Buyru Nur
Department of Medical Biology, Istanbul University, Cerrahpasa Medical Faculty;
Exp Ther Med. 2012 Dec;4(6):1092-1096. doi: 10.3892/etm.2012.715. Epub 2012 Sep 18.
Aberrant methylation of gene promoter regions is one of the mechanisms for inactivation of tumor suppressor genes in human malignancies. In this study, the methylation pattern of 24 tumor suppressor genes was analyzed in 75 samples of ovarian cancer using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Of the 24 tumor suppressor genes examined, aberrant methylation was observed in 17. The three most frequently methylated genes were CDKN2B, CDH13 and RASSF1, followed by ESR1 and MLH1. Methylation frequencies ranged from 1.3% for CDKN2A, RARβ, CASP8, VHL and TP73 to 24% for CDKN2B. The corresponding normal DNA from each patient was also investigated. Methylation was detected in tumors, although not in normal tissues, with the exception of two samples, indicating aberrant methylation in tumors. Clear cell carcinoma samples exhibited a higher frequency of CDKN2B promoter hypermethylation compared to those of other histological types (P=0.05). Our data indicate that methylation of the CDKN2B gene is a frequent event in ovarian carcinogenesis and that analysis of only three genes is sufficient to detect the presence of methylation in 35% of ovarian cancer cases. However, more studies using a much larger sample size are needed to define the potential role of DNA methylation as a marker for ovarian cancer.
基因启动子区域的异常甲基化是人类恶性肿瘤中抑癌基因失活的机制之一。在本研究中，使用甲基化特异性多重连接依赖探针扩增（MS-MLPA）分析法，对75例卵巢癌样本中24个抑癌基因的甲基化模式进行了分析。在所检测的24个抑癌基因中，有17个出现了异常甲基化。甲基化频率最高的三个基因是CDKN2B、CDH13和RASSF1，其次是ESR1和MLH1。甲基化频率范围从CDKN2A、RARβ、CASP8、VHL和TP73的1.3%到CDKN2B的24%。还对每位患者相应的正常DNA进行了研究。除两个样本外，肿瘤中检测到甲基化，而正常组织中未检测到，表明肿瘤中存在异常甲基化。与其他组织学类型相比，透明细胞癌样本中CDKN2B启动子高甲基化的频率更高（P = 0.05）。我们的数据表明，CDKN2B基因的甲基化在卵巢癌发生过程中是常见事件，仅分析三个基因就足以在35%的卵巢癌病例中检测到甲基化的存在。然而，需要更多使用更大样本量的研究来确定DNA甲基化作为卵巢癌标志物的潜在作用。
