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Accepted Articles of Congress

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  • Merkel Cell Polyomavirus Large T-Antigen Mutations in Merkel Cell Carcinoma Pathogenesis: A Systematic Review

  • Alireza Pourrahim,1,* Mohammad Mahdi Pourrahim,2 Omid Raiesi,3 Alireza Vasiee,4
    1. Student Research Committee, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
    2. Student Research Committee, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
    3. Omid Raiesi
    4. Department of Nursing, Faculty of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran


  • Introduction: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin malignancy frequently driven by Merkel cell polyomavirus (MCPyV) integration. Viral large T-antigen (LT-Ag) truncating mutations disable replication yet preserve oncogenic domains, promoting tumor initiation and progression. We synthesized available data on the prevalence of LT-Ag mutations and their impact on tumor biology and patient outcomes in MCC.
  • Methods: We searched PubMed, EMBASE, Scopus, and Web of Science up to June 2025 using (“Merkel cell carcinoma” AND “polyomavirus” AND “large T antigen” AND (“mutation” OR “truncation”)). Inclusion criteria were clinical or translational studies reporting LT-Ag mutation frequency, mutation type, survival associations, or in vitro functional assays. Two reviewers independently screened records, extracted data on mutation prevalence, hazard ratios (HRs), and proliferation indices, and assessed study quality with the Newcastle–Ottawa Scale for clinical cohorts and SYRCLE’s RoB for preclinical models.
  • Results: Nine studies (6 clinical cohorts, n = 312 MCC patients; 3 cell-based assays, n = 45) met inclusion criteria. Pooled prevalence of LT-Ag truncating mutations in MCPyV-positive tumors was 72.3% (95% CI 65.4–78.6). Truncating events represented 89.1% of all LT-Ag alterations (95% CI 83.8–93.0). Patients harboring truncating LT-Ag mutations experienced worse overall survival (HR 1.82; 95% CI 1.45–2.29; p < 0.02) and disease-free survival (HR 1.67; 95% CI 1.31–2.13; p = 0.002). In vitro studies demonstrated that LT-Ag truncations increased MCC cell proliferation by a mean ratio of 1.43 (95% CI 1.27–1.60; p < 0.01). No significant publication bias or high heterogeneity was observed.
  • Conclusion: LT-Ag truncating mutations are highly prevalent in MCPyV-positive MCC and associate with accelerated tumor cell proliferation and approximately twofold increased risk of mortality and recurrence. These data highlight LT-Ag mutation profiling as a prognostic biomarker and a rationale for therapies targeting viral oncoprotein functions.
  • Keywords: Merkel cell carcinoma; Merkel cell polyomavirus; large T-antigen; truncating mutation

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