Frequent occurrence of RASSF1A promoter hypermethylation and merkel cell polyomavirus in merkel cell carcinoma

• Published in: Molecular carcinogenesis Vol. 48; no. 10; pp. 903 - 909
• Main Authors: Helmbold, Peter, Lahtz, Christoph, Enk, Alexander, Herrmann-Trost, Peter, Marsch, Wolfgang Ch, Kutzner, Heinz, Dammann, Reinhard H.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2009
• Subjects: Acid Anhydride Hydrolases - genetics; Carcinoma, Merkel Cell - genetics; Carcinoma, Merkel Cell - virology; Cyclin-Dependent Kinase Inhibitor p16 - genetics; DNA methylation; DNA Methylation - genetics; DNA, Viral - genetics; DNA-Binding Proteins - genetics; epigenetics; Humans; Neoplasm Proteins - genetics; Nuclear Proteins - genetics; Polymerase Chain Reaction; Polyomavirus; Polyomavirus - isolation & purification; Polyomavirus Infections - genetics; Polyomavirus Infections - virology; Promoter Regions, Genetic - genetics; Receptor-Like Protein Tyrosine Phosphatases, Class 5 - genetics; Retrospective Studies; Simian virus 40; Simian virus 40 - genetics; skin cancer; Skin Neoplasms - genetics; Skin Neoplasms - virology; Tumor Protein p73; tumor suppressor gene; Tumor Suppressor Proteins - genetics; virus infection
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.20540

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. © 2009 Wiley‐Liss, Inc.