Research Article

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

  1. Peter Helmbold1,*,
  2. Christoph Lahtz2,
  3. Alexander Enk1,
  4. Peter Herrmann-Trost3,
  5. Wolfgang Ch. Marsch4,
  6. Heinz Kutzner5,
  7. Reinhard H. Dammann2,*

Article first published online: 26 MAR 2009

DOI: 10.1002/mc.20540

Issue

Molecular Carcinogenesis

Molecular Carcinogenesis

Volume 48, Issue 10, pages 903–909, October 2009

Additional Information

How to Cite

Helmbold, P., Lahtz, C., Enk, A., Herrmann-Trost, P., Marsch, W. Ch., Kutzner, H. and Dammann, R. H. (2009), Frequent occurrence of RASSF1A promoter hypermethylation and merkel cell polyomavirus in merkel cell carcinoma. Mol. Carcinog., 48: 903–909. doi: 10.1002/mc.20540

Author Information

  1. 1

    Department of Dermatology, University of Heidelberg, Heidelberg, Germany

  2. 2

    Institute for Genetics, University of Giessen, Giessen, Germany

  3. 3

    Institute of Pathology, Halle, Germany

  4. 4

    Department of Dermatology, University of Halle, Halle, Germany

  5. 5

    DermPath, Friedrichshafen, Germany

*Department of Dermatology, University of Heidelberg, D-69115 Heidelberg, Germany.

  1. †

    Peter Helmbold and Christoph Lahtz contributed equally to this work.

Publication History

  1. Issue published online: 21 SEP 2009
  2. Article first published online: 26 MAR 2009
  3. Manuscript Accepted: 18 FEB 2009
  4. Manuscript Revised: 17 FEB 2009
  5. Manuscript Received: 11 DEC 2008

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Keywords:

  • skin cancer;
  • tumor suppressor gene;
  • virus infection;
  • DNA methylation;
  • epigenetics

Abstract

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.

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