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NIH Research Festival

September 23 – 25, 2024

XMEN disease increases cutaneous MCPyV viral burden and elevates the risk of early onset Merkel cell carcinoma

Authors

  • Y Saito
  • N Mohsin
  • J Strong
  • AJ Jabbour
  • P Nghiem
  • CB Buck
  • DV Pastrana
  • J Bergerson
  • S Conlan
  • AF Freeman
  • JA Segre
  • HH Kong
  • I Brownell

Abstract

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer frequently caused by Merkel cell polyomavirus (MCPyV). The median age for MCC diagnosis is 75 years old, and MCC is vanishingly rare in patients under 40 years old. We describe three patients with X-linked immuno-deficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (XMEN) who developed MCC before age 25 years old. XMEN disease is a rare immunodeficiency associated with lymphoma and caused by mutations in the magnesium transporter 1 (MAGT1) gene. All three patients presented with advanced stage MCC, and all had MCPyV positive tumors. Cutaneous microbiome sampling revealed elevated levels of MCPyV in patients with XMEN disease and specific defects in controlling other polyomavirus infections. Moreover, these patients had elevated titers for neutralizing antibodies against MCPyV and other polyomaviruses. Remarkably, one patient with XMEN disease who underwent allogeneic hematopoietic cell transplant continued to have elevated cutaneous MCPyV levels even after engraftment and discontinuation of immunosuppression, suggesting that virus susceptibility was due, in part, to MAGT1 defects in non-hematopoietic cells. Although, immunosuppression increases MCC incidence, XMEN disease is associated with a risk for early onset MCC not observed in other primary immunodeficiencies, further supporting the hypothesis that non-immune risk factors for MCPyV are contributing to the risk for MCC. These results demonstrate that early onset MCC is a component of XMEN disease that appears to be related to defective control of polyomavirus infection.

Scientific Focus Area: Cancer Biology

This page was last updated on Tuesday, August 6, 2024

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Current Research Festival

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