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Aberrant Promoter Hypermethylation of RASSF Family Members in Merkel Cell Carcinoma
Institute for Genetics, University of Giessen, Giessen D-35392, Germany
Institute of Pathology, Halle D-06097, Germany
Department of Dermatology, University of Halle, Halle D-06120, Germany
DermPath, Friedrichshafen D-88048, Germany
Department of Dermatology, University of Heidelberg, Heidelberg D-69120, Germany
* Author to whom correspondence should be addressed.
Received: 11 September 2013; in revised form: 23 October 2013 / Accepted: 8 November 2013 / Published: 18 November 2013
Abstract: 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.
Keywords: merkel cell; tumor suppressor; DNA methylation; epigenetics; RASSF
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Richter, A.M.; Haag, T.; Walesch, S.; Herrmann-Trost, P.; Marsch, W.C.; Kutzner, H.; Helmbold, P.; Dammann, R.H. Aberrant Promoter Hypermethylation of RASSF Family Members in Merkel Cell Carcinoma. Cancers 2013, 5, 1566-1576.
Richter AM, Haag T, Walesch S, Herrmann-Trost P, Marsch WC, Kutzner H, Helmbold P, Dammann RH. Aberrant Promoter Hypermethylation of RASSF Family Members in Merkel Cell Carcinoma. Cancers. 2013; 5(4):1566-1576.
Richter, Antje M.; Haag, Tanja; Walesch, Sara; Herrmann-Trost, Peter; Marsch, Wolfgang C.; Kutzner, Heinz; Helmbold, Peter; Dammann, Reinhard H. 2013. "Aberrant Promoter Hypermethylation of RASSF Family Members in Merkel Cell Carcinoma." Cancers 5, no. 4: 1566-1576.