Acral melanoma (AM) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and non-acral cutaneous melanoma (NAM) in Asians are not well understood.

To augment the understanding of the prevalence, patterns, and associations of various mutations between different subtypes of melanoma.

We performed comprehensive genomic profiling of 409 cancer-associated genes, using next-generation sequencing, in 66 primary melanomas comprised of 45 AMs and 21 NAMs.

Most of the AMs (27/45, 60%), but only 5 of 21 (23·8%) NAMs were the Triple wild-type (Triple-WT) tumors. Compared with the AMs, the NAMs exhibited a significantly higher frequency of BRAF mutation. Meanwhile, the frequencies of NRAS/KRAS mutations, cell cycle aberrations, copy number gains of BIRC2/3/5, and gains of receptor tyrosine kinase genes were significantly higher in the AMs. Ulceration was found at significantly higher rates in the AMs and NAMs with cell cycle aberrations and gains of receptor tyrosine kinase genes. Notably, cell cycle aberrations and copy number gains of BIRC2/3/5 were significantly associated with poor melanoma-specific survival in all 66 melanoma patients and especially in the 45 AM patients. Furthermore, a multivariate analysis showed that lymph node metastasis and cell cycle aberrations were independent prognostic factors for melanoma-specific survival.

This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AMs and NAMs in Asians. This article is protected by copyright. All rights reserved.