ArticleFrontiers in medicine2026
Locus-specific HERV expression identifies an aggressive, NK-depleted, checkpoint-refractory acral melanoma phenotype.
Article in Frontiers in medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Acral melanoma (AM) is a non-ultraviolet (non-UV)-derived subtype of cutaneous melanoma that is associated with worse survival outcomes compared to UV-driven melanomas. AM tumors exhibit distinct molecular characteristics and poor responses to immune checkpoint blockade. Hitherto, the role of transposable elements (TEs), particularly human endogenous retroviruses (HERVs), in AM progression remains incompletely characterized. Methods: We quantified locus-specific TE expression from RNA sequencing (RNA-seq) of 36 AM samples from 33 patients and integrated the results with clinical outcomes, a pathologist-reviewed purity covariate, and immune cell deconvolution. Results: A three-locus HERV signature, composed of Conclusion: Our findings reframe AM as a transcriptomically stratifiable disease, define a locus-specific HERV signature of aggressive, checkpoint-refractory AM, and nominate a structurally intact, pan-HLA-presentable HERV-K antigen candidate for further evaluation.
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