Genetic variability and integration of Merkel cell polyomavirus in Merkel cell carcinoma

Merkel cell polyomavirus (MCPyV) is associated to Merkel cell carcinoma (MCC). We studied 113 MCC tumoral skin lesions originating from 97 patients. MCPyV detection was higher in fresh-frozen (FF) biopsies (94%) than in formalin-fixed paraffin-embedded biopsies (39–47%). Mean viral load in FF tumor was of 7.5 copies per cell with a very wide range (0.01–95.4). Nineteen complete sequences of LTAg were obtained, mainly from FF biopsies when the viral load was high. Seventeen showed stop codons, all localized downstream of the pRb protein binding domain. Sequence comparison and phylogenetic analysis showed that all sequences clustered in the large C clade of MCPyV strains. MCPyV integration was demonstrated in 19 out of 27 FF MCC DNA biopsies without evidence of specific host cellular genome integration site. In 13/19 cases, the viral junction was located within the second exon of the LTAg, after the pRB binding domain.

► We studied a series of 97 patients with Merkel cell carcinoma (MCC).
► MCPyV mean viral load in fresh-frozen tumors was of 7.5 copies per cell (0.01 – 95.4).
► A stop codon in helicase domain was present in 89.5 % (17/19) of MCPyV large T Ag.
► MCPyV sequences had a low variability and clustered in the large Caucasian clade.
► MCPyV integration was demonstrated in the majority of the MCC tumors.