Merkel Cell Polyomavirus and DNA Damage Response (DDR): Transcriptional Analysis of DDR Pathways in the Context of Merkel Cell Carcinoma.

Background/Objectives: Merkel cell polyomavirus (MCPyV) is a ubiquitous virus strictly associated with Merkel cell carcinoma (MCC), a rare and aggressive skin cancer. MCPyV oncogenic properties are associated mainly with early protein expression, integration, and LT truncation. MCPyV can also interact with DNA Damage Response (DDR) mechanisms, contributing to oncogenesis and tumor progression. In this work, we investigated the correlation between MCPyV and MCC and evaluated the mRNA expression profiles of DDR genes in virus-positive and -negative tumors. Methods: A total of 19 formalin-fixed paraffin-embedded biopsies were acquired from patients diagnosed with MCC. After DNA and RNA extraction, the DNA was used for MCPyV detection via qPCR and for sequencing analysis of the early, late, and non-coding control viral regions and the extracted RNA was used for MCPyV transcripts, miRNA detection and for the evaluation of several DDR genes expression such as ATM, ATR, CHK1, CHK2, H2AX, Rad51, p53, and p21, in MCPyV-positive and -negative samples via reverse transcription, PCR, and qPCR. Results: MCPyV presence was detected in 11/19 samples, all characterized by viral integration, LT truncation, and early region expression only. Furthermore, higher mRNA levels of DDR genes were observed in MCPyV-positive tumors compared with the negative ones. Conclusions: Our findings support the role of MCPyV in MCC formation and suggest its involvement in the transcriptional regulation of DDR genes, which may influence tumor progression. Understanding the molecular interplay between MCPyV and the DDR may guide future research into plausible novel diagnostic and therapeutic strategies for virus-induced tumors.