1. Whole genome sequencing elucidates etiological differences in MCPyV-negative Merkel cell carcinoma.
- Author
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Stephan C, Al Assaad M, Levine MF, Deshpande A, Sigouros M, Manohar J, Sboner A, Elemento O, Pavlick AC, and Mosquera JM
- Subjects
- Humans, Male, Aged, Female, Mutation, Aged, 80 and over, Middle Aged, Carcinoma, Merkel Cell genetics, Carcinoma, Merkel Cell virology, Carcinoma, Merkel Cell pathology, Skin Neoplasms genetics, Skin Neoplasms virology, Skin Neoplasms pathology, Merkel cell polyomavirus genetics, Merkel cell polyomavirus isolation & purification, Whole Genome Sequencing
- 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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Max F. Levine and Aditya Deshpande are employees at Isabl, Inc. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)
- Published
- 2024
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