RASSF1A and CDH1 hypermethylation as potential epimarkers in breast cancer
RASSF1A and CDH1 hypermethylation as potential epimarkers in breast cancer
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DOI：
10.3233/cbm-2012-0230
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发表时间：
2011-01-01
影响因子：
3.1
通讯作者：
Fridrichova, Ivana
中科院分区：
文献类型：
--
作者：
Sebova, Katarina;Zmetakova, Iveta;Fridrichova, Ivana
乳腺癌是全球女性最常见的癌症，占所有女性恶性肿瘤的28.2%。除了遗传变化外，表观遗传事件，如异常DNA甲基化和组蛋白修饰，也是癌症发生的原因。许多肿瘤抑制基因的失活是由DNA超甲基化引起的，这可以用于鉴定新的表观遗传生物标志物。为了探讨DNA甲基化水平与乳腺癌进展之间的关系，我们分别从92例乳腺癌患者和50例对照组的石蜡包埋肿瘤组织和血液样本中，采用定量多重甲基化特异性PCR分析了RASSF 1A和CDH 1启动子的DNA甲基化。采用Kruskal-Wallis和货车der Waerden方差分析检验RASSF 1A和CDH 1甲基化水平与临床病理参数之间的相关性。在92例乳腺癌患者中，76例（82.6%）表现出不同水平的RASSF 1A（范围为1.20 - 92.63%）和20例（21.7%）CDH 1（范围为1.20 - 79.62%）甲基化。然而，在50名对照中没有发现甲基化。在肿瘤大小、淋巴结状态和TNM分期中观察到RASSF 1A甲基化的增加趋势，但只有CDH 1甲基化水平在淋巴结状态和IHC亚型的患者亚组之间显示出统计学显著差异。总体而言，稳定的相对较高的RASSF 1A甲基化可用作通用肿瘤标志物，频率较低但高度甲基化的CDH 1启动子可用于鉴定潜在的转移性肿瘤。
Breast cancer is the most common cancer in women worldwide, representing 28.2% of all female malignancies. In addition to genetic changes, epigenetic events, as aberrant DNA methylation and histone modification, are responsible for cancer development. Many tumour suppressor genes are inactivated by DNA hypermethylation, which could be utilized for identification of new epigenetic biomarkers. To investigate the relation between DNA methylation level and breast cancer progression, we analysed DNA methylation in RASSF1A and CDH1 promoters using quantitative multiplex methylation-specific PCR in paraffin-embedded tumour tissues and blood samples from 92 breast cancer patients and 50 controls, respectively. The associations between RASSF1A and CDH1 methylation levels and clinico-pathological parameters were tested by Kruskal-Wallis and van der Waerden ANOVA tests. Out of 92 breast cancer patients, 76 (82.6%) manifested various levels of RASSF1A (range from 1.20 to 92.63%) and 20 (21.7%) of CDH1 (range from 1.20 to 79.62%) methylation. However, no methylation was found in 50 controls. Increasing trends in RASSF1A methylation were observed in tumour size, lymph node status and TNM stage, but only CDH1 methylation levels showed statistically significant differences between the patient subgroups in lymph node status and IHC subtype. Overall, stable relatively high RASSF1A methylation could be utilised as universal tumour marker and the less frequent but highly methylated CDH1 promoter can serve for identification of potentially metastasising tumours.