Laboratory of Epigenetics, Cancer Research Institute and Brain Korea 2nd Stage, Seoul National University, Seoul, Korea.
J Korean Med Sci. 2010 Aug;25(8):1152-9. doi: 10.3346/jkms.2010.25.8.1152. Epub 2010 Jul 20.
Promoter CpG island hypermethylation has become recognized as an important mechanism for inactivating tumor suppressor genes or tumor-related genes in human cancers of various tissues. Gene inactivation in association with promoter CpG island hypermethylation has been reported to be four times more frequent than genetic changes in human colorectal cancers. Hepatocellular carcinoma is also one of the human cancer types in which aberrant promoter CpG island hypermethylation is frequently found. However, the number of genes identified to date as hypermethylated for hepatocellular carcinoma (HCC) is fewer than that for colorectal cancer or gastric cancer, which can be attributed to fewer attempts to perform genome-wide methylation profiling for HCC. In the present study, we used bead-array technology and coupled methylation-specific PCR to identify new genes showing cancer-specific methylation in HCC. Twenty-four new genes have been identified as hypermethylated at their promoter CpG island loci in a cancer-specific manner. Of these, TNFRSF10C, HOXA9, NPY, and IRF5 were frequently hypermethylated in hepatocellular carcinoma tissue samples and their methylation was found to be closely associated with inactivation of gene expression. Further study will be required to elucidate the clinicopathological implications of these newly found DNA methylation markers in hepatocellular carcinoma.
启动子 CpG 岛甲基化已被认为是人类各种组织癌症中失活肿瘤抑制基因或肿瘤相关基因的重要机制。与启动子 CpG 岛甲基化相关的基因失活在人类结直肠癌中比遗传变化更为常见，报道称其频率高出四倍。肝癌也是异常启动子 CpG 岛甲基化频繁发生的人类癌症类型之一。然而，迄今为止，确定为肝癌（HCC）甲基化的基因数量少于结直肠癌或胃癌，这归因于对 HCC 进行全基因组甲基化谱分析的尝试较少。在本研究中，我们使用珠阵列技术和甲基化特异性 PCR 来鉴定在 HCC 中以癌症特异性方式显示出甲基化的新基因。已经鉴定出 24 个新基因在其启动子 CpG 岛位点以癌症特异性方式发生甲基化。其中，TNFRSF10C、HOXA9、NPY 和 IRF5 在肝癌组织样本中频繁发生甲基化，并且发现其甲基化与基因表达的失活密切相关。需要进一步研究来阐明这些新发现的肝癌 DNA 甲基化标志物在临床病理方面的意义。
