ArticleActa neuropathologica communications2025
A comprehensive, multi-center, immunogenomic analysis of melanoma brain metastases.
Article in Acta neuropathologica communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- The paracrine effects of tumor cells on endothelial cells and macrophages in brain metastases with different primary sites.Frontiers in immunology · 2026Article
- The Neuro-Melanoma Singularity: Convergent Evolution of Neural and Melanocytic Networks in Brain Metastatic Adaptation.Biomolecules · 2025Review
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Authors and funding
16 authors.
Funding
Abstract
backgroundMelanoma brain metastases (MBM) have a unique molecular profile compared to extracranial metastases (ECM). Description of the biological features and clinical outcomes of MBM will facilitate the design of rational therapies.
methodsWe examined the mutational landscape and gene expression profiles of MBM (74 patients) and ECM (34 patients) in paired patient samples from a previously published dataset with whole-exome sequencing (WES) and RNA sequencing (RNAseq) data from MD Anderson Cancer Center (MDACC). We also present findings from MBM from a new cohort of 14 patients from Duke University to strengthen investigation of somatic mutations and gene expression profiles. Gene Set Enrichment Analysis (GSEA) was used to compare paired MBM versus lymph node (LN) metastases and skin metastases. Relative immune cell abundance was inferred using deconvolution methods. Survival outcomes from craniotomy and associations with biological features, BRAF mutation status, and PTEN expression were assessed.
resultsGSEA found that autophagy signaling pathways are enriched in MBM versus LN and skin metastases. BRAF was the most frequently mutated clinically relevant gene in MBM and ECM, with NRAS and PTEN also frequently altered in MBM. The most strongly upregulated genes in autophagy pathways were glial fibrillary acidic protein (GFAP) and hemoglobin beta (HBB). An increased proportion of immune-suppressive M2 compared to tumor-suppressive M1 macrophages in MBM and ECM was identified. There was not sufficient evidence for an association between BRAF V600 mutation status or expression and overall survival (OS) from craniotomy.
conclusionsThe mutational landscape and gene expression of MBM from the Duke cohort resembled those previously reported in the MDACC cohort. Upregulation of autophagy pathways was observed in patient-matched MBM versus LN and skin metastases due to upregulation of two genes, GFAP and HBB. In MBM, higher M2:M1 ratio may contribute to a therapeutically relevant immune-suppressive tumor microenvironment (TME).
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