This study developed a mouse model of Merkel cell carcinoma (MCC) by expressing Merkel cell polyomavirus small T antigen (sT-Ag) and suppressing Trp53 specifically in SOX9+ hair follicle progenitor cells, to investigate MCC cell of origin and tumor initiation.
sT-Ag expression combined with Trp53 attenuation in SOX9+ hair follicle cells produced metastatic neuroendocrine tumors recapitulating the histopathologic and immunophenotypic features of human MCC; sT-Ag alone induced partial MCC-associated gene expression but p53 suppression was required for full neuroendocrine lineage transdifferentiation.
This is a mouse model and may not fully recapitulate human MCC biology; the study does not directly test the role of the large T antigen (LT-Ag) in tumor initiation; findings are limited to SOX9+ hair follicle progenitors and do not rule out other cells of origin.
This immunocompetent de novo MCC mouse model provides a platform for preclinical testing of MCC therapies and offers mechanistic insight into the cooperative roles of viral T antigens and p53 loss in MCC initiation — but direct clinical application awaits further translational studies.
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