Spatial Analysis Reveals Gene Expression and Microenvironmental Changes in the Transition of Nevus to Melanoma
Cancer Research, vol. 86, pp. 4400–4413
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.
Authors 9
-
Inger Z. M. Kreuger Aachen
Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center 1 Department of Dermatology, , Leiden, the Netherlands
Leiden University Medical Center 2 Leiden Center for Computational Oncology, , Leiden, the Netherlands
-
Veerle A. Merkus Aachen
Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center 1 Department of Dermatology, , Leiden, the Netherlands
-
Sanne de Haan Aachen
Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center 1 Department of Dermatology, , Leiden, the Netherlands
-
Anne M.R. Schrader Aachen
Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center 3 Department of Pathology, , Leiden, the Netherlands
-
Ferenc A. Scheeren Aachen
Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center 1 Department of Dermatology, , Leiden, the Netherlands
-
Leiden University Medical Center · Oncode Institute
Affiliation as printed
Leiden University Medical Center 4 Department of Medical Oncology, Oncode Institute, , Leiden, the Netherlands
-
Tim van Groningen Aachen
Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center 1 Department of Dermatology, , Leiden, the Netherlands
Leiden University Medical Center 2 Leiden Center for Computational Oncology, , Leiden, the Netherlands
-
Leiden University Medical Center · Oncode Institute
Affiliation as printed
Leiden University Medical Center 2 Leiden Center for Computational Oncology, , Leiden, the Netherlands
Leiden University Medical Center 4 Department of Medical Oncology, Oncode Institute, , Leiden, the Netherlands
-
Remco van Doorn Aachen
Leiden University Medical Center · The Netherlands Cancer Institute
Affiliation as printed
5Department of Dermatology, Netherlands Cancer Institute, Amsterdam, the Netherlands
Leiden University Medical Center 1 Department of Dermatology, , Leiden, the Netherlands
Leiden University Medical Center 2 Leiden Center for Computational Oncology, , Leiden, the Netherlands
Cited by 0 stored of 0
No patents citing this paper on Lens.org (checked 2026-10-11).