Investigation of mrna expression levels of dna damage response genes in merkel cell polyomavirus-positive merkel cell carcinoma. A pilot study

Merkel Cell Polyomavirus (MCPyV) is recognized as the major aetiological agent of Merkel Cell Carcinoma (MCC), an aggressive skin tumor. MCPyV-mediated oncogenesis is strictly dependent on viral integration and the expression of a truncated form of the Large T Antigen (LT). Moreover, like other oncogenic DNA viruses, MCPyV may interfere with the DNA damage response (DDR) machinery, thus promoting genomic instability and tumorigenesis. Therefore, the objective of this study was to characterize MCPyV infection in 7 MCC patients and to elucidate the plausible role of the virus in the DDR pathway. MCPyV DNA was detected in 3/7 MCC patients and, as expected, viral integration and LT truncation were observed in virus-positive MCCs, along with the expression of early genes only. Over-expression of DDR genes such as ATM, ATR and their downstream kinases Chk1 and Chk2 was reported in MCPyV-positive MCCs supporting the potential role of the virus in interfering with DDR. Our findings support the established viral aetiology of MCC, and describe, for the first time, an over-expression of DDR components in MCPyV-positive MCC, laying the basis for future studies aimed at investigating the contribution of this pathway to MCPyV-mediated carcinogenesis and exploring the plausible clinical implications of host DDR factors for the treatment of MCC.