The presence of mutations of BRAF, NRAS, and KIT genes is recognized as playing a role during carcinogenesis. Our study aims to evaluate and review other studies that present the frequency of mutations of BRAF, NRAS, and KIT genes for different populations, and analyse correlation to their clinical-pathological characteristics and to the demographics of melanoma. Thirty-two articles were selected from a collection of published literature studying 6299 patients. The parameters for correlation to different variables were calculated by odds ratio, for random and single effects. 38.5% of patients present BRAF gene mutations, 16.4% in NRAS, and 10% in KIT. Mutations of the BRAF gene were correlated to superficial spreading melanoma (odds ratio = 1.31), localization in the torso (odds ratio = 1.42) and presence of metastases. Mutations in NRAS were correlated to nodular melanoma (odds ratio = 1.57), localized in the limbs (odds ratio = 1.31). Mutations of the KIT gene were correlated to mucosal melanoma (odds ratio = 1.59). Populations in Brazil, the US, Sweden, Italian, and Australia were found to be correlated to mutations of BRAF and melanoma. Populations in Italy, Sweden, Spain, and the US were found to be correlated to mutations of NRAS. Populations in Japan, China, Turkey, Canada, and Russia were found to be correlated to mutations of KIT. Data correlated to the presence of melanoma and population type is due to the amount of studies performed across of globe.

Introduction. Melanoma is the most aggressive type of skin cancer, with poor prognosis in advanced stages. The incidence and mortality rates have increased in recent years. Single nucleotide polymorphisms p.R24P, p.M53I, p.G101W, p.V126D, and p.A148T in the CDKN2A (HGNC ID: 1787) gene have been associated with the development of melanoma in different populations; however, this association has not been studied in Colombia. Methods. Cutaneous melanoma patients and healthy controls (85 cases and 166 controls) were included in this study. These subjects were screened through HRM-qPCR assay and detected variants in exon 1 and 2 of CDKN2A gene and confirmed with Sanger sequencing. Chi-square test was used to compare allele and genotype distributions between cases and controls. Odds ratio (OR) with 95% confidence interval (CI) was calculated to determine the association between polymorphisms and haplotypes with melanoma susceptibility. Statistical and haplotype analyses were performed using Stata® and R-Studio®. Results. Fifty-four percent of women were identified both in cases and controls. The frequencies of melanoma subtypes were 36,47% lentigo maligna, 24,71% acral lentiginous, 23,53% superficial extension, and 15,29% nodular. Variants in the CDKN2A gene were 11.76% in cases and 8.43% in controls. The most frequent was p.A148T in 5.88% of cases and in 4.82% of controls. GGTTG haplotype showed statistically significant differences between cases and controls ( p value = 0.04). Conclusion. CDKN2A polymorphisms p.G101W, p.R24P, p.M53I, and A148T are not associated with melanoma susceptibility in the Colombian population; further studies regarding genetic interaction and additive effects between more variants are required.

Objectives Genetic association studies on alopecia areata (AA) performed in various populations have shown heterogeneous results. The aim of the current review was to synthesize the results of said studies to estimate the impact of FAS, FASL, PTPN22, CTLA4 and IL2RA gene polymorphisms on AA susceptibility. Design A systematic literature search was conducted in the Medline, Web of Science, Scopus, EMBASE and LILACS databases. Studies published up to June 2020 were included. The results available in the grey literature including the Open Grey and Google Scholar databases were also used. The texts of potentially related studies were screened by individual reviewers. Evidence of publication bias was assessed using the Newcastle-Ottawa scale and the quality of evidence was assessed using the GRADE system. The quantitative synthesis was performed using the fixed effect model. Results Out of 1784 articles, we identified 18 relevant articles for the qualitative synthesis and 16 for the quantitative synthesis. In a study of rs2476601 polymorphism of PTPN22 gene, including 1292 cases and 1832 controls, a correlation was found with the risk of developing AA in the allelic model (OR1.49 [95% C:1.13–1.95]), the heterozygous codominant (OR1.44 [95% CI:1:19–1.76]) and dominant model (OR1.43 [95% CI:1.18–1.73]). No association was found between the presence of FASL, PTPN22, CTLA and IL2RA gene polymorphisms with AA susceptibility. Conclusions The results suggest that the T allele of the single nucleoid polymorphism (SNP) rs2476601 in PTPN22 gene is a risk factor for developing alopecia areata. However, more robust studies defining the ethnic background of the population of origin are required, so that the risk identified in the present study can be validated. Additionally, a greater number of studies is necessary to evaluate the role of the FAS, FASL, PTPN22, CTLA4 and IL2RA genetic variants, given the heterogenous results found in the literature.

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.