RESUMO
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.
Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Melanoma/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Colômbia , Éxons , Feminino , Frequência do Gene , Genes p16 , Predisposição Genética para Doença , Genética Populacional , Genótipo , Haplótipos , Heterozigoto , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
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.
Assuntos
GTP Fosfo-Hidrolases/genética , Melanoma/genética , Proteínas de Membrana/genética , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-kit/genética , Neoplasias Cutâneas/genética , Linhagem Celular Tumoral , Colômbia , Análise Mutacional de DNA/métodos , Éxons/genética , Células HT29 , Humanos , Taxa de Mutação , Raios Ultravioleta/efeitos adversos , Melanoma Maligno CutâneoRESUMO
El carcinoma escamocelular (CEC) ocupa el segundo puesto en frecuencia entre los cánceres de la de piel. Un grupo de CEC tiene un comportamiento biológico muy agresivo, y cursa con recurrencia local, metástasis y muerte. El evento etiológico principal es la radiación ultravioleta que induce el daño del DNA de los queratinocitos, especialmente en las personas blancas. Hay muchas variantes clínicas, cada una de ellas con un comportamiento biológico diferente. De igual modo, existen infinidad de variantes histológicas, pero la clasificación más adecuada es la que se basa en el patrón de crecimiento, porque éste refleja el comportamiento biológico y está en estrecha relación con el pronóstico. Tanto las características clínicas como las de histopatología son la base para que el dermatólogo decida el tratamiento óptimo en cada caso.