Frequent Occurrence of RASSF1A Promoter Hypermethylation and Merkel Cell Polyomavirus in Merkel Cell Carcinoma
Frequent Occurrence of RASSF1A Promoter Hypermethylation and Merkel Cell Polyomavirus in Merkel Cell Carcinoma
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DOI：
10.1002/mc.20540
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发表时间：
2009-10-01
影响因子：
4.6
通讯作者：
Dammann, Reinhard H.
中科院分区：
文献类型：
--
作者：
Helmbold, Peter;Lahtz, Christoph;Dammann, Reinhard H.
默克尔细胞癌（MCC）是最具侵袭性的皮肤癌之一。最近有报道称，默克尔细胞多瘤病毒（MCPyV）在MCC中发生在受体酪氨酸磷酸G型（PTPRG）基因中的整合，并且病毒感染与癌症中肿瘤抑制基因（TSG）的表观遗传沉默相关。为了研究TSG失活与MCC中病毒感染之间是否存在相关性，我们通过PCR研究了98个MCC中RASSF 1A、TP 73、PTPRG、FHIT和CDKN 2A启动子的超甲基化以及MCPyV和SV 40的存在。83例MCC中有42例（51%）经常发现RASSF 1A高甲基化。41例MCC中9例（22%）存在CDKN 2A甲基化。在MCC中，TP 73（0%）、PTPRG（4%）和FHIT（0%）的高甲基化并不常见。有趣的是，在98个MCC中的90个（92%）中发现MCPyV，然而，未检测到SV 40信号。本研究结果提示，MCC中存在RASSF 1A基因的高甲基化和MCPyV的存在，这些事件可能参与了MCC的发病机制。(C)2009威利-利斯公司
Merkel cell carcinoma (MCC) is one of the most aggressive cancers of the skin. It has recently been reported that integration of a Merkel cell polyomavirus (MCPyV) in receptor tyrosine phosphates type G (PTPRG) gene occurs in MCC, and that viral infections are associated with epigenetic silencing of tumor suppressor genes (TSG) in cancer. To examine whether a correlation between TSG inactivation and viral infection can be found in MCC, we investigated the promoter hypermethylation of RASSF1A, TP73, PTPRG, FHIT, and CDKN2A and the presence of MCPyV and SV40 in 98 MCC by PCR. Hypermethylation of RASSF1A was frequently found in 42 of 83 (51%) of MCC. Methylation of CDKN2A was present in 9 of 41 (22%) of MCC. Hypermethylation of TP73 (0%), PTPRG (4%), and FHIT (0%) was infrequent in MCC. Interestingly, MCPyV was found in 90 of 98 (92%) MCC, however, no SV40 signal was detected. No correlation between TSG hypermethylation and viral infection was found. Our results show frequent hypermethylation of RASSF1A and the presence of MCPyV in primary MCC, and that these events may contribute to the pathogenesis of MCC. (C) 2009 Wiley-Liss, Inc.