Data from Spatial Analysis Reveals Gene Expression and Microenvironmental Changes in the Transition of Nevus to Melanoma

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Abstract A third of melanomas originate from benign melanocytic nevi, representing a transition between distinct stages of melanocytic neoplasia. To gain insight into the transcriptional and microenvironmental changes accompanying this transition, we used spatially resolved, transcriptome-wide analysis combined with imaging mass cytometry on nevus-associated melanomas. The transcriptional alterations were multifaceted, broadly spanning three principal processes: increased proliferation coupled with metabolic adaptation, enrichment of melanocytic lineage-associated programs, and remodeling of the microenvironment. Proliferative activity in melanoma was marked by increased CDK2 expression. Alterations in the nevus and melanoma transcriptomes were accompanied by microenvironmental changes, including shifts in cellular composition and altered gene expression in keratinocytes and fibroblasts. Within the nevus, CD163+ M2-like macrophages were present, with few other infiltrating or surrounding immune cells. In contrast, melanoma regions were surrounded by abundant immune cells, including M1-like macrophages expressing chemokine genes and T cells bearing markers of repeated activation. Simultaneously, melanomas exhibited features associated with an immunosuppressive microenvironment. This study presents a spatial atlas of the nevus-to-melanoma transition, advancing our understanding of the transcriptomic shifts and local immune environment that characterize melanoma initiation. Significance: Identification of key transcriptional and microenvironmental shifts during nevus-to-melanoma transition through comprehensive spatial profiling provides a foundation for understanding melanoma initiation and guiding future biological and clinical investigations.

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