Molecular pathogenesis of Merkel cell carcinoma

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer which is twice as lethal as melanoma as more than one-third of MCC patients will die from this cancer. Although MCC, which primarily affects elderly and immune suppressed individuals, is very rare to date, its incidence is rapidly increasing. In contrast to the immense progress that has been made in the elucidation of the molecular pathogenesis of other cancer entities, until recently there were no clear-cut indications which events drive the carcinogenesis of MCC. Important findings published last year have changed this radically. Hypermethylation of the p14(ARF) promoter and a striking correlation between expression of p63 and the clinical course of MCC have been reported. Most important, however, is the discovery that MCC development in the majority of cases is preceded by the integration of genomic sequences of the hitherto unknown Merkel cell polyomavirus (MCPyV). Now a fundamental improvement in the understanding of MCC pathogenesis as well as the development of new therapeutic approaches based on this knowledge appear to be possible within the near future.