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- W4366184890 abstract "Background: Melanocytic tumors exhibit a wide variety of morphologies and gene expression patterns. The genetic and molecular mechanisms that underly this heterogeneity — as well as those that promote malignancy — are not well understood. Transcriptomic spatial profiling, however, offers a relatively new and exciting means to visualize intratumoral, differential gene expression. Objective: To utilize high-plex in situ hybridization to spatially characterize gene expression at single-cell resolution in benign and malignant melanocytic proliferations. To examine how melanocyte gene expression profiles differ between tissue microenvironments in neoplasms with multiple morphologies, with particular emphasis on cyclin-dependent kinase (CDK) related genes previously implicated in melanomagenesis. Methods: We performed high-plex in situ hybridization with fluorescent molecular barcodes directed at ∼1000 genes in a variety of melanocytic proliferations, including tumors with multiple morphologies and melanomas negative for PRAME (PReferentially expressed Antigen in MElanoma). Selected targets were confirmed using immunohistochemistry (IHC) and subsequently analyzed for prognostic value using survival data from The Cancer Genome Atlas. Results: We detected over 190,000 cells using high-plex in situ hybridization with an average of ∼130 unique genes per cell; unique niches were revealed by uniform manifold approximation and projection (UMAP), supervised cell clustering using a skin reference profile, and unsupervised clustering approaches. Using a candidate approach, we developed differential gene expression maps of dermal-epidermal junction and dermal melanocytes of benign and malignant tumors, with emphasis on MITF, PMEL (HMB-45), PRAME, CDKN2A (P16), and CDK2, which were then subjected to Gene Ontology (GO) enrichment analysis. Conclusions: Melanocytic tumor gene expression heterogeneity can be visualized using high-plex in situ hybridization at the single-cell level. Our data have revealed unique, spatially restricted expression profiles of cyclins and cyclin-dependent kinases within primary and metastatic melanomas." @default.
- W4366184890 created "2023-04-19" @default.
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- W4366184890 date "2023-05-01" @default.
- W4366184890 modified "2023-09-28" @default.
- W4366184890 title "1201 Single-cell, spatial profiling of heterogeneous melanocytic neoplasms" @default.
- W4366184890 doi "https://doi.org/10.1016/j.jid.2023.03.1215" @default.
- W4366184890 hasPublicationYear "2023" @default.
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