biostudies-literatureLi YNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC)National Key Research and Development Program of China (NKPs)National Key Research and Development Program of China2495-2514https://www.ebi.ac.uk/biostudies/studies/S-EPMC12163602biostudies-literatureUnknown31(12)<h4>Purpose</h4>To identify the specific intratumoral and microenvironmental heterogeneity of acral melanoma (AM) and mucosal melanoma (MM), we aimed to delineate their distinct cellular compositions, evolutionary trajectories, and subtype-specific therapeutic strategies.<h4>Experimental design</h4>Single-cell transcriptomic and genomic landscapes were analyzed across 42 melanoma (28 AM, 11 MM, and 3 nonacral cutaneous melanoma) samples, supplemented by in vitro and in vivo validation. Tumor and stromal cells were profiled using single-cell RNA sequencing, whole-exome sequencing, and functional assays, including transwell migration, co-culture systems, and xenograft models.<h4>Results</h4>Tumor cells exhibited divergent evolutionary routes, with MM dominated by MGP+/PCOLCE+ subpopulations Clinical cancer research : an official journal of the American Association for Cancer ResearchSingle-Cell Transcriptomic Landscape Deciphers Intratumoral Heterogeneity and Subtypes of Acral and Mucosal Melanomas.PMC121636022021YFA11010002021YFA1101004U21A20379Li CJia DChen JMa XWei ZZhang RYu HWang KCui RQian WRen GLi YZhang ZLi TZhang YCui ZChen WMiao XChen YSong XShi JXu ZZhou JGoding CRfalseSingle-Cell Transcriptomic Landscape Deciphers Intratumoral Heterogeneity and Subtypes of Acral and Mucosal Melanomas.<h4>Purpose</h4>To identify the specific intratumoral and microenvironmental heterogeneity of acral melanoma (AM) and mucosal melanoma (MM), we aimed to delineate their distinct cellular compositions, evolutionary trajectories, and subtype-specific therapeutic strategies.<h4>Experimental design</h4>Single-cell transcriptomic and genomic landscapes were analyzed across 42 melanoma (28 AM, 11 MM, and 3 nonacral cutaneous melanoma) samples, supplemented by in vitro and in vivo validation. Tumor and stromal cells were profiled using single-cell RNA sequencing, whole-exome sequencing, and functional assays, including transwell migration, co-culture systems, and xenograft models.<h4>Results</h4>Tumor cells exhibited divergent evolutionary routes, with MM dominated by MGP+/PCOLCE+ subpopulations 2025-01-01T00:00:00Z2025 Jun2026-06-02T22:28:46.031Z2026-04-21T03:13:34.368ZS-EPMC121636024019273710.1158/1078-0432.CCR-24-3164