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Distinct genomic features in a retrospective cohort of mucosal, acral, and vulvovaginal melanomas. | LitMetric
Background : Compared with sun-exposed melanomas, less is known regarding the pathogenesis of sun-protected melanomas. Sun-protected melanomas share many epidemiologic factors, but their genetic heterogeneity is not well studied.Objective : We investigated the genomic profile of acral, mucosal, and vulvovaginal melanomas. We hypothesize that mucosal melanomas, recognized for their uniquely aggressive clinical behavior, have distinct genomic features.Methods : We performed whole transcriptome messenger RNA and DNA (1711 genes) sequencing, messenger RNA expression profiling, tumor mutational burden, ultraviolet signature, and copy number variants analysis on 29 volar/digital acral, 7 mucosal, and 6 vulvovaginal melanomas.Results : There was significant genetic heterogeneity, particularly in acral melanomas, with 36% having BRAF alterations, whereas other melanomas had none (P = .0159). Nonzero ultraviolet signatures were more frequent in acral melanomas, suggesting greater ultraviolet involvement. Mucosal melanomas formed a distinct group with increased expression of cell cycle and proliferation genes. Various targetable aberrations were identified, such as AURKA and ERBB2, in mucosal and acral melanomas, respectively.Limitations : The sample size was a small.Conclusion : There is significant genetic heterogeneity among sun-protected melanomas. Mucosal melanomas have upregulation in cell cycle and proliferation genes, which may explain their aggressive behavior. Ultraviolet radiation plays some role in a subset of acral but not other melanomas.
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