title: Frequent detection of Merkel cell polyomavirus in human Merkel cell carcinomas and identification of a unique deletion in the VP1 gene.
abstract: Merkel cell carcinoma (MCC) is a rare but very aggressive human malignancy of the elderly or immunosuppressed patients. Recently, the clonal integration of a new human polyoma virus, which was termed Merkel cell polyomavirus (MCPyV), has been reported in 8 of 10 MCC patients. In the present study, we studied the formalin-fixed and paraffin-embedded tissue specimens of 39 MCC for the presence of MCPyV by PCR. We applied four different primer sets directed against the large T antigen and the VP1 gene of MCPyV. We were able to detect MCPyV in 77% (n = 30) of MCC as confirmed by sequence analyses of the PCR products. Sequence analyses showed only minor nucleotide changes compared with the previously published MCC sequences. In addition, one patient revealed the amplification of two PCR products using PCR primers directed against the VP1 gene. Sequence analyses confirmed the presence of the expected 351-bp PCR product and in addition a second PCR product of 261 bp containing a unique 90-bp deletion in the VP1 gene, which will lead to a predicted loss of 28 amino acids. The unique 90-bp deletion within the VP1 gene possibly is a result of incomplete viral integration of MCPyV in the MCC. The presence of MCPyV in the majority of MCC tissue specimens in our study strongly underlines a possible role for MCPyV as an etiologic agent in the carcinogenesis of MCC.
authors.affiliation: Institute of Pathology, University Hospital Freiburg, and Center for Dermatopathology, Freiburg, Germany.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Kassem
authors.forename: Anja
authors.initials: A
authors.lastname: Schöpflin
authors.forename: Carlos
authors.initials: C
authors.lastname: Diaz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weyers
authors.forename: Elmar
authors.initials: E
authors.lastname: Stickeler
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.forename: Axel
authors.initials: A
authors.lastname: Zur Hausen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D036022:Capsid Proteins / Q000235:genetics*; D015266:Carcinoma, Merkel Cell / Q000150:complications / Q000821:virology*; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D018862:Merkel Cells / Q000821:virology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D011120:Polyomavirus / Q000235:genetics; D027601:Polyomavirus Infections / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology*; D015995:Prevalence; D017386:Sequence Homology, Amino Acid; D012878:Skin Neoplasms / Q000150:complications / Q000821:virology*
chemical_list: D036022:Capsid Proteins; D004279:DNA, Viral; C062481:VP1 protein, polyomavirus