Mutations in the BRAF, NRAS, and C-KIT Genes of Patients Diagnosed with Melanoma in Colombia Population

Abstract

Introduction. Mutations in the BRAF, NRAS, and C-KIT genes have been associated with the histopathological characteristics of melanoma. Likewise, the incidence of each of these subtypes changes according to the geographical origin of the population analyzed. Objective. To determine the mutation frequency in exons 11 and 15 of the BRAF gene, exons 1 and 2 of the NRAS gene, and exons 11, 13, and 17 of the C-KIT gene and to relate it with histological subtypes in patients from a region with high levels of ultraviolet radiation. Methodology. The clinicopathological characteristics of 54 cutaneous melanoma samples were analyzed. Mutation analysis was performed via qPCR on paraffin-embedded tumor tissue samples using probes specific for the V600E mutation. Amplification of exons 11 and 15 of the BRAF gene, exons 1 and 2 of the NRAS gene, and exons 11, 13, and 17 of the C-KIT gene was performed for subsequent sequencing using the Sanger method. Result. The most frequent histological subtype in the analyzed sample was lentigo maligna/lentigo maligna melanoma (52%) followed by acral lentiginous melanoma (20%). The BRAF-V600 variant was the most frequent (63.6%). The most frequent (54%) mutation in NRAS was p.Lys5∗. In the C-KIT gene, only the Val560Ala mutation was found. Conclusion. Differences in histological subtypes and mutations in the BRAF, NRAS, and C-KIT genes were found in the analyzed population. This indicates that environmental and genetic factors significantly influence the introduction of the disease in this geographic region.

Frequency of BRAF V600E/E2/D and V600K/R/M mutations in patients with malignant melanoma unresectable stage III-IIIC–IV from May to August-2021 at Unigem in Medellin

“…Of the total sample, 62.3% were men, and male pre-dominance was maintained in all melanoma subtypes, being more marked in nodular and acral lentiginous (26.0 and 12.5%, respectively). This differs slightly from that reported in the literature, where there is usually a slightly higher incidence in women and in Lentigo Maligna, results that do not agree with previous local studies 10,11 but do with international research 12,13 Similar to that reported globally are also observed in relation to the mean age which ranges between 57-63 years of age 14,15 however a study conducted in Japan reported an increase in cases in populations under 50 years 9 as illustrated in Table 1.…”

3’UTR-CDKN2A and CDK4 Germline Variants Are Associated With Susceptibility to Cutaneous Melanoma

“…An interesting aspect is that reported subtypes of melanoma in the Latin-American region are different to those reported in high-incidence regions. In the Colombian population, several studies have shown that lentigo malignant melanoma is the most frequent with 36.41-52%, followed by acral lentiginous melanoma with 20-24.71% incidence (15). The frequency of melanoma in Latin America varies according to the studied population.…”

Five-Year Follow-Up of POLARIS-01 Phase II Trial: Toripalimab as Salvage Monotherapy in Chinese Patients With Advanced Melanoma

“…In addition, previous studies indicated the mutually exclusive mutations among BRAF, NRAS, and NF1. 10-12 In terms of 10 patients with KIT mutation in the present study, 2 had NF1 mutations, while neither of them had BRAF and NRAS mutations. Median follow-up duration was 16.9 months (range, 0.9-70.1).…”