Merkel 细胞癌中 RASSF 家族成员启动子异常甲基化。
Aberrant Promoter Hypermethylation of RASSF Family Members in Merkel Cell Carcinoma.
机构信息
Institute for Genetics, University of Giessen, Giessen D-35392, Germany.
出版信息
Cancers (Basel). 2013 Nov 18;5(4):1566-76. doi: 10.3390/cancers5041566.
Merkel cell carcinoma (MCC) is one of the most aggressive cancers of the skin. RASSFs are a family of tumor suppressors that are frequently inactivated by promoter hypermethylation in various cancers. We studied CpG island promoter hypermethylation in MCC of RASSF2, RASSF5A, RASSF5C and RASSF10 by combined bisulfite restriction analysis (COBRA) in MCC samples and control tissue. We found RASSF2 to be methylated in three out of 43 (7%), RASSF5A in 17 out of 39 (44%, but also 43% in normal tissue), RASSF5C in two out of 26 (8%) and RASSF10 in 19 out of 84 (23%) of the cancer samples. No correlation between the methylation status of the analyzed RASSFs or between RASSF methylation and MCC characteristics (primary versus metastatic, Merkel cell polyoma virus infection, age, sex) was found. Our results show that RASSF2, RASSF5C and RASSF10 are aberrantly hypermethylated in MCC to a varying degree and this might contribute to Merkel cell carcinogenesis.
默克尔细胞癌（Merkel cell carcinoma，MCC）是皮肤最具侵袭性的癌症之一。RASSFs 是肿瘤抑制因子家族，在多种癌症中常因启动子 hypermethylation 而失活。我们通过联合亚硫酸氢盐限制性分析（combined bisulfite restriction analysis，COBRA）研究了 MCC 中 RASSF2、RASSF5A、RASSF5C 和 RASSF10 的 CpG 岛启动子 hypermethylation。我们发现 43 个 MCC 样本中有 3 个（7%）的 RASSF2 发生甲基化，39 个中有 17 个（44%，但正常组织中也有 43%）的 RASSF5A 发生甲基化，26 个中有 2 个（8%）的 RASSF5C 发生甲基化，84 个中有 19 个（23%）的 RASSF10 发生甲基化。未发现分析的 RASSFs 的甲基化状态之间或 RASSF 甲基化与 MCC 特征（原发性与转移性、Merkel 细胞多瘤病毒感染、年龄、性别）之间存在相关性。我们的结果表明，RASSF2、RASSF5C 和 RASSF10 在 MCC 中不同程度地发生异常 hypermethylation，这可能有助于 Merkel 细胞癌的发生。
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