Mutational profiling of acral melanomas in Korean populations

Abstract

The proportion of acral melanoma (AM) is much higher in Asian populations than in Caucasian populations. Although mutational profiles associated with AM have been discovered in Caucasian populations, knowledge of its genetic alterations in Asian populations is limited. To describe the molecular nature of AM in Korean patients, we performed mutational profiling of AM and matched normal tissues in patients. Fifty-one formalin-fixed paraffin-embedded AM samples and 32 matched pairs from patients' saliva DNA were analysed by next-generation sequencing. Only mutations confirmed via digital droplet PCR or in BRAF, KIT and NRAS, the most frequently altered cancer genes in cutaneous melanoma, were considered as positive. The relationship between mutational status and clinicopathological features were examined. Of the 47 AM patients screened, alteration of BRAF, NRAS and KIT genes was observed in 6.4%, 4.3% and 8.5%, respectively. We also tested matched normal tissues of patients to identify tumor-specific mutations. Examination of the mutational profile in a cohort of 28 primary melanomas and matched normal controls found BRAF mutations in two cases (7.1%), KIT mutations in three cases (10.7%) and CTNNB1 mutations in one case (3.6%). The BRAF, NRAS and KIT mutation status did not correlate with clinicopathological characteristics. Our results show that KIT, NRAS and BRAF hotspot mutations occur at a low frequency in Korean populations. We also observed a case with the CTNNB1 mutation, which raises the possibility that other pathways are associated with AM development.

Genetic alterations in primary melanoma in Taiwan

“… In contrast, the NRAS mutation rates in AMs reported in this study were similar to those described in other Asian studies. Compared with the overall results from Asian populations, KIT and KRAS mutations were found to be more prevalent in AMs in our study population . In addition to underlying ethnic disparities, these differences may have been due, in part, to the AMs in our study being composed of only acral lentiginous melanomas.…”

“…However, AMs account for 50–70% of all cases of melanoma in Asians . Although several genomic profiling studies of melanoma have been conducted, the number of AM cases in those studies was limited . Furthermore, a comprehensive comparison of genomic alterations between AMs and nonacral melanomas (NAMs) in Asians has not been conducted, and the associations between structural variants and clinical outcomes have not been characterized.…”

Genetic Alterations in Primary Acral Melanoma and Acral Melanocytic Nevus in Korea: Common Mutated Genes Show Distinct Cytomorphological Features

“…Thus, mutation was not found to be associated with a specific anatomical site on the plantar surface. Our study showed a much higher frequency of BRAF V600E mutations in acral melanoma than was found in previous Asian studies (Jin et al, 2013;Sakaizawa et al, 2015;Shim et al, 2017;Si et al, 2012). These differences might be explained by the improvement in detection tools, by the selection of deeper melanomas showing variable cytology and mixed cellularity of various morphologies, and by the genes included in the test panels.…”

Mutation profile of primary subungual melanomas in Caucasians

“…Although other studies of SUM present a higher percentage of 30-50% [25,32] or no detected among 13 SUM patients [29]. In HFM/ALM, KIT mutations are frequent -occurring in 8.5-36% of tumors usually as a substitution of a single amino acid in exon 11, 13, or 17 [6,[8][9][10][30][31][32][33][34]. Siroy et al sequenced 54 patients with advanced acral melanoma and reported KIT mutation in 11% of cases [5].…”