Mutation profile of primary subungual melanomas in Caucasians

Background: Specific genomic profile of cutaneous melanomas is related to UVR exposure, which exerts biological and therapeutic impact. Subungual melanoma (SUM) is an exceedingly rare disease; therefore, it is not well characterized. SUM pathogenesis is not related to UVR induced DNA damage and expected to differ from other melanoma subtypes. Our study aimed to define the mutation profile of SUM in Caucasians. Materials and Methods: Next-generation sequencing-based genomic analysis was used to identify frequently mutated loci in 50 cancer-related genes in 31 SUM primary tumors. Results: The most abundant mutations in SUM were found in KIT – in 13% of cases and NRAS – also in 13%, while BRAF - only in 3% of cases. Conclusions: Our findings confirmed a high frequency of KIT and NRAS mutations in SUM, as well as a low incidence of BRAF mutations. We reported novel KRAS, CTNNB1, TP53, ERBB2, and SMAD4 mutations in SUM. Our findings provide new insights into the molecular pathogenesis of SUM.