Identification of genetic mutations related to invasion and metastasis of acral melanoma via whole-exome sequencing.

Many studies have analyzed the genes related to melanoma. However, only a limited number of studies have been conducted to identify the genes that are involved in the invasion and metastasis of acral melanoma (AM). Here, we attempted to investigate the genetic mutations associated with invasion and metastasis of AM. We analyzed five multi-regional samples of primary and metastatic AM and histologically normal tissue adjacent to the tumor (NAT) in two AM patients by whole-exome sequencing (WES). We identified single nucleotide variations and small indels present in tissue samples but not in saliva. We compared the sequencing results of superficial and deep lesions and primary and metastatic lesions of AM. We identified significantly deleterious mutations (SDM) that are likely to be related to invasion and metastasis of AM, respectively. SDM such as SKA3, MAST4, CNNM1, KIAA1549L, and SLC26A10 were found only in the deep lesion, but not in the superficial lesion. SDM present only in the metastatic lesion were ANO1, CPEB1, EP300, INADL, MAP1B, MAP7D1, MARCH6, NETO1, PRKCE, SBK1, TNRC6A, USP13, WDR74, and ZNF827. In conclusion, we applied multi-region WES to investigate possible pathogenic mutations related to invasion and metastasis in AM. Several genes including CNNM1, USP13, ZNF827, WDR74, CPEB1, and EP300 might be related to invasion and metastasis of AM. This study might facilitate the exploration of the evolutionary pathogenesis of advanced AM.