Merkel cell polyomavirus in naevoid basal cell carcinoma syndrome-associated basal cell carcinomas and sporadic trichoblastomas

Abstract

Merkel cell carcinoma (MCC) is a very aggressive neuroendocrine non-melanoma skin cancer (NMSC) of elderly or immunosuppressed individuals [ [1] Swann M.H. Yoon J. Merkel cell carcinoma. Semin Oncol. 2007; 34: 51-567 Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar ]. Approximately 80% of MCC harbor the recently detected Merkel cell polyomavirus (MCPyV) within the tumor DNA [ [2] Feng H. Shuda M. Chang Y. Moore P.S. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008; 319: 1096-1100 Crossref PubMed Scopus (2328) Google Scholar ]. MCPyV-positive MCC reveal tumor specific truncating mutations within the large T antigen (LTAg) of MCPyV which are not found in the MCPyV wildtype [ [3] Shuda M. Feng H. Kwun H.J. et al. T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus. Proc Natl Acad Sci USA. 2008; 105: 16272-16277 Crossref PubMed Scopus (553) Google Scholar ]. Thus epidemiology, clonal integration and tumor specific mutations within the LTAg of MCPyV are strongly supporting an important role of MCPyV in the etiopathogenesis of human MCC. However, the presence of MCPyV has been reported in NMSC of immunosuppressed and immunocompetent patients, including squamous cell carcinomas (SCC), Bowen's disease (BD) and basal cell carcinoma (BCC) [ 4 Kassem A. Technau K. Kurz A.K. et al. Merkel cell polyomavirus sequences are frequently detected in nonmelanoma skin cancer of immunosuppressed patients. Int J Cancer. 2009; 125: 356-361 Crossref PubMed Scopus (122) Google Scholar , 5 Becker J.C. Houben R. Ugurel S. Trefzer U. Pföhler C. et al. MC Polyomavirus is frequently present in Merkel cell carcinoma of European patients. J Invest Dermatol. 2009; 129: 248-250 Crossref PubMed Scopus (282) Google Scholar , 6 Wieland U. Mauch C. Kreuter A. Krieg T. Pfister H. Merkel cell polyomavirus DNA in persons without Merkel cell carcinoma. Emerg Infect Dis. 2009; 15: 1496-1498 Crossref PubMed Scopus (115) Google Scholar , 7 Andres C, Belloni B, Puchta U, Sander CA, Flaig MJ. Prevalence of MCPyV in Merkel cell carcinoma and non-MCC tumors. J Cutan Pathol 2009; July 14 PMID: 19615033. Google Scholar ]. BCCs are among the most common malignant skin tumors and show differentiation towards germinative cells of the hair follicle. In addition to sporadic forms, BCCs may occur in the context of the naevoid basal cell carcinoma syndrome (NBCCS) which is a rare disease with an autosomal dominant trait with high penetrance and variable phenotype. The underlying molecular causes of NBCCS are germline mutations of the tumor suppressor gene PTCH1 located on the long arm of chromosome 9q22.3 [ [8] Johnson R.L. Rothman A.L. Xie J. Goodrich L.V. Bare J.W. Bonifas J.M. et al. Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science. 1996; 272: 1668-1671 Crossref PubMed Scopus (1624) Google Scholar ]. It is of interest that sporadic trichoblastoma which is a relatively rare benign counterpart of BCC, also showing differentiation toward germinative cells of the hair follicle, has been linked to chromosome 9p22.3 [ [9] Matt D. Xin H. Vortmeyer A.O. Zhuang Z. Burg G. Boni R. Sporadic trichoepithelioma demonstrates deletions at 9q22.3. Arch Dermatol. 2000; 136: 657-660 Crossref PubMed Scopus (55) Google Scholar ].