ArticleDiscover oncology2025
Identification of candidate susceptibility genes for cutaneous malignant melanoma through integrated multi-method analysis.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 authors.
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Abstract
backgroundCutaneous malignant melanoma (CMM) is a deadly skin cancer with genetic basis. Although genome-wide association studies (GWAS) have identified various risk loci, their functional consequences remain largely undefined. This study aims to uncover novel CMM-associated genes and investigate their potential biological mechanisms by integrating large-scale genetic and transcriptomic datasets.
methodsWe combined CMM GWAS summary statistics with gene expression data from GTEx v8 and conducted transcriptome-wide association studies (TWAS) across multiple tissues. Key genes were further examined using MAGMA-based gene-level analysis, Bayesian fine-mapping, Mendelian randomization (MR), and colocalization to infer potential causality. Functional associations were explored via GeneMANIA network analysis.
resultsTwo genes, TMEM184B and MAFF, were repeatedly identified across analytical approaches. TMEM184B emerged as a novel gene associated with melanoma risk. Both MR (P < 0.05) and colocalization (PP.H4 > 0.8) provided consistent evidence of causal links between gene expression and CMM susceptibility. Functional network analysis implicated TMEM184B in transmembrane ion transport and MAPK signaling pathways, while MAFF was linked to oxidative stress response pathways.
conclusionThis study identifies TMEM184B as a previously unreported risk gene for CMM and reaffirms the relevance of MAFF in disease predisposition. These findings advance our understanding of melanoma's genetic architecture and highlight specific, high-priority genes and pathways for future experimental investigation, suggesting they may serve as potential therapeutic targets.
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