Global gene expression analysis in macrophages expressing BRAFV600E and in ECD lesion tissue. (A) Principal component analysis (PCA) of transcriptional profiles of primary human macrophages or of macrophages transduced with wtBRAF and BRAFV600E 6 days after transduction. (B) Unsupervised clustering analysis of DEGs in macrophages expressing BRAFV600E compared with controls (native and transduced with wtBRAF combined). (C) Volcano plots highlighting significant downregulated (green) and upregulated (red) genes in macrophages expressing BRAFV600E compared with controls (native and transduced with wtBRAF combined). (D) PCA of transcriptional profiles of matched PBMCs and ECD lesions from patients carrying the BRAFV600E mutation. (E) Unsupervised clustering analysis of DEGs in matched PBMCs and ECD lesions from patients carrying the BRAFV600E mutation. (F) Volcano plots highlighting significant downregulated (green) and upregulated (red) genes in matched PBMCs and ECD lesions from patients carrying the BRAFV600E mutation. (G) GSEA against Hallmark Gene Sets from Molecular Signatures Database (v7.1) showing enriched gene signatures identified in ECD lesions compared with matched PBMCs from patients (left) and in macrophages carrying BRAFV600E compared with controls (native and transduced with wtBRAF combined; right); NES, normalized enrichment score. (H) GSEA plot graph showing the concordance of the top upregulated gene signatures identified in macrophages carrying BRAFV600E compared with controls (native and transduced with BRAFwt combined) and in ECD lesions compared with matched PBMCs from patients.