Location of Repository

Quantitative Analysis of Viral Load per Haploid Genome Revealed the Different Biological Features of Merkel Cell Polyomavirus Infection in Skin Tumor

By Satoshi Ota, Shumpei Ishikawa, Yutaka Takazawa, Akiteru Goto, Takeshi Fujii, Ken-ichi Ohashi and Masashi Fukayama


Merkel cell polyomavirus (MCPyV) has recently been identified in Merkel cell carcinoma (MCC), an aggressive cancer that occurs in sun-exposed skin. Conventional technologies, such as polymerase chain reaction (PCR) and immunohistochemistry, have produced conflicting results for MCPyV infections in non-MCC tumors. Therefore, we performed quantitative analyses of the MCPyV copy number in various skin tumor tissues, including MCC (n = 9) and other sun exposure-related skin tumors (basal cell carcinoma [BCC, n = 45], actinic keratosis [AK, n = 52], Bowen’s disease [n = 34], seborrheic keratosis [n = 5], primary cutaneous anaplastic large-cell lymphoma [n = 5], malignant melanoma [n = 5], and melanocytic nevus [n = 6]). In a conventional PCR analysis, MCPyV DNA was detected in MCC (9 cases; 100%), BCC (1 case; 2%), and AK (3 cases; 6%). We then used digital PCR technology to estimate the absolute viral copy number per haploid human genome in these tissues. The viral copy number per haploid genome was estimated to be around 1 in most MCC tissues, and there were marked differences between the MCC (0.119–42.8) and AK (0.02–0.07) groups. PCR-positive BCC tissue showed a similar viral load as MCC tissue (0.662). Immunohistochemistry with a monoclonal antibody against the MCPyV T antigen (CM2B4) demonstrated positive nuclear localization in most of the high-viral-load tumor groups (8 of 9 MCC and 1 BCC), but not in the low-viral-load or PCR-negative tumor groups. These results demonstrated that MCPyV infection is possibly involved in a minority of sun-exposed skin tumors, including BCC and AK, and that these tumors display different modes of infection

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:3386999
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles



    1. (2001). Aberrant methylation and simian virus 40 tag sequences in malignant mesothelioma.
    2. (2009). Array-CGH reveals recurrent genomic changes in Merkel cell carcinoma including amplification of L-Myc.
    3. (2011). Association of Merkel cell polyomavirus infection with morphologic differences in Merkel cell carcinoma.
    4. (2009). Association of Merkel cell polyomavirus–specific antibodies with Merkel cell carcinoma.
    5. (2009). Clinical factors associated with Merkel cell polyomavirus infection in Merkel cell carcinoma.
    6. (2008). Clonal integration of a polyomavirus in human Merkel cell carcinoma.
    7. (2010). Comparable expression and phosphorylation of the retinoblastoma protein in Merkel cell polyoma virus–positive and negative Merkel cell carcinoma.
    8. (2010). Cozzio A
    9. (2009). Detection of Merkel cell polyomavirus in Merkel cell carcinoma and Kaposi’s sarcoma.
    10. (1983). DNA-binding properties of simian virus 40 T-antigen mutants defective in viral DNA replication.
    11. (1982). Enhanced transformation of human fibroblasts by origin-defective simian virus 40.
    12. (2008). Frequent detection of Merkel cell polyomavirus in human Merkel cell carcinomas and identification of a unique deletion in the VP1 gene.
    13. (2009). Frequent occurrence of RASSF1A promoter hypermethylation and Merkel cell polyomavirus in Merkel cell carcinoma.
    14. (2010). Grundhoff A
    15. (2009). Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors.
    16. (2011). Human Merkel cell polyomavirus small T antigen is an oncoprotein targeting the 4E-BP1 translation regulator.
    17. (2009). Keme ´ny L
    18. (2010). Lack of evidence for basal or squamous cell carcinoma infection with Merkel cell polyomavirus in immunocompetent patients with Merkel cell carcinoma.
    19. (1981). Loss of functional large T-antigen and free viral genomes from cells transformed in vitro by polyoma virus after passage in vivo as tumor cells.
    20. (2008). Mathematical analysis of copy number variation in a DNA sample using digital PCR on a nanofluidic device. PLoS. One 3: e2876 Merkel Cell Polyomavirus Infection in Skin Tumor PLoS
    21. (2009). MC polyomavirus is frequently present in Merkel cell carcinoma of European patients.
    22. (2009). Merkel cell carcinoma of the skin: pathological and molecular evidence for a causative role of MCV in oncogenesis.
    23. (2010). Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression.
    24. (2010). Merkel cell carcinoma: our experience with seven patients in Korea and a literature review.
    25. (2010). Merkel cell polyomavirus DNA detection in lesional and nonlesional skin from patients with Merkel cell carcinoma or other skin diseases.
    26. (2009). Merkel cell polyomavirus DNA in persons without Merkel cell carcinoma.
    27. (2009). Merkel cell polyomavirus expression in Markel cell carcinomas and its absence in combined tumors and pulmonary neuroendocrine carcinomas.
    28. (2009). Merkel cell polyomavirus is more frequently present in North American than Australian Merkel cell carcinoma tumors.
    29. (2009). Merkel cell polyomavirus sequences are frequently detected in nonmelanoma skin cancer of immunosuppressed patients.
    30. (2009). Merkel cell polyomavirus strains in patients with Merkel cell carcinoma.
    31. (2010). Prevalence of MCPyV in Merkel cell carcinoma and non-MCC tumors.
    32. (2009). Prevalence of Merkel cell polyomavirus in Merkel cell carcinoma.
    33. (2002). Progressive aberrant methylation of the RASSF1A gene in simian virus 40 infected human mesothelial cells.
    34. (2010). Quantitative detection of Merkel cell virus in human tissues and possible mode of transmission.
    35. (2011). Replication, gene expression and particle production by a consensus Merkel Cell Polyomavirus (MCPyV) genome.
    36. (2006). Sarasin A
    37. (2009). Screening of the specific polyoma virus as diagnostic and prognostic tools for Merkel cell carcinoma.
    38. (1984). Simian virus 40 large T-antigen point mutants that are defective in viral DNA replication but competent in oncogenic transformation.
    39. (2008). T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus.
    40. (2009). The presence of polyomavirus in nonmelanoma skin cancer in organ transplant recipients is rare.
    41. (2009). Ultrastructural proof of polyomavirus in Merkel cell carcinoma tumour cells and its absence in small cell carcinoma of the lung.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.