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Updated: Jun 10, 2025
Merkel Cell Polyomavirus Infection and Detection
Published on: February 7, 2019
Whole genome sequencing elucidates etiological differences in MCPyV-negative Merkel cell carcinoma
Carla Stephan1, Majd Al Assaad2, Max F Levine3
1Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
Abstract:
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine neoplasm of the skin. Immunosuppression, ultraviolet radiation and the integration of Merkel cell polyomavirus (MCPyV) have all been shown to be involved in the pathogenesis of this malignancy. We performed whole genome sequencing on two MCPyV-negative cases of MCC that demonstrated very different clinical presentations and outcomes, and mutational profiles. The first case exhibited a highly aggressive clinical course, absence of UV-signature mutations and a low tumor mutational burden. A rearrangement in the tumor suppressor gene SUFU was identified, a likely driver and potential target of the Hedgehog signaling pathway. Meanwhile, the second case exhibited a less aggressive behavior, harbored UV-signature mutations, and a high mutational burden including mutations in TP53 and RB1.
Insights
We sequenced two Merkel cell carcinoma (MCC) cases lacking Merkel cell polyomavirus (MCPyV). One case showed aggressive progression with a SUFU gene rearrangement, while the other had a less aggressive course with TP53 and RB1 mutations.
Area of Science:
- Oncology
- Genomics
- Dermatology
Background:
- Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer.
- Pathogenesis involves immunosuppression, UV radiation, and Merkel cell polyomavirus (MCPyV).
- Understanding genetic drivers in MCPyV-negative MCC is crucial for targeted therapies.
Purpose of the Study:
- To investigate the genomic landscape of Merkel cell carcinoma (MCC) in Merkel cell polyomavirus (MCPyV)-negative cases.
- To identify potential driver mutations and signaling pathways involved in distinct clinical presentations of MCC.
- To compare mutational profiles between MCC cases with differing clinical courses and outcomes.
Main Methods:
- Whole genome sequencing was performed on two Merkel cell carcinoma (MCC) samples negative for Merkel cell polyomavirus (MCPyV).
- Comparative analysis of mutational profiles, including tumor mutational burden and specific mutation signatures (e.g., UV-signature mutations).
- Identification and characterization of genetic alterations in key tumor suppressor and signaling pathway genes.
Main Results:
- Case 1: Highly aggressive MCC, low tumor mutational burden, absence of UV-signature mutations, and a SUFU gene rearrangement implicated in Hedgehog pathway signaling.
- Case 2: Less aggressive MCC, high tumor mutational burden, presence of UV-signature mutations, and mutations in TP53 and RB1 tumor suppressor genes.
- Distinct genomic profiles correlate with differing clinical behaviors in MCPyV-negative Merkel cell carcinoma.
Conclusions:
- Genomic heterogeneity significantly influences Merkel cell carcinoma (MCC) progression, even in the absence of Merkel cell polyomavirus (MCPyV).
- SUFU alterations represent a potential driver in aggressive, UV-mutation-negative MCC.
- TP53 and RB1 mutations are associated with high mutational burden and UV-driven MCC, suggesting distinct therapeutic vulnerabilities.
