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Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine malignancy of the skin with an annual incidence in the United States of 0.34 and 0.17 per 100,000 men and women, respectively. MCC incidence increases with age, is higher among men and whites, and positively correlates with solar ultraviolet (UV) index, suggesting UV radiation exposure may play a role in the development of MCC. MCC incidence rates are also higher among severely immunosuppressed populations, including people who have undergone organ transplantation, have lymphoma, and are HIV-infected. Given the increased risk for MCC observed with immunosuppression and the established associations between viral infections and other cancers that occur more often in immunosuppressed populations, MCC was a prime cancer candidate for a viral cause. Subsequent investigation discovered a genome encompassing 5387 base pairs of a new polyomavirus, subsequently named the Merkel cell polyomavirus.