BRAF and NRAS Mutations and the Association with Prognosis of Acral Lentiginous and Nodular Melanomas in Indonesia

Background: Melanomas are rare yet the most aggressive skin cancer among Asians. Clinical presentation, risk factors, and the underlying molecular mechanisms are strikingly different from cutaneous melanoma in Caucasians. Methods: Mutation patterns of BRAF and NRAS genes were examined from DNAs derived from primary melanoma tumor tissues (fresh tissues or formalin-fixed paraffin-embedded samples) using pyrosequencing. Results: A total of 63 patients consisting of acral lentiginous melanoma (N=22, 34.9) and nodular melanoma (N=41, 65.1) were included in this study. Most patients were diagnosed at Stage III-IV (N=49, 77.8), Breslow thickness more than 4 mm (N=51, 80.9), presence of ulceration (N=35, 55.6), diameter larger than 6 mm (N=61, 96.8), regional node infiltration (N=41, 77.8). BRAF and NRAS mutations were found in 28 (44.4) and 8 (12.7), respectively. BRAF and NRAS mutations were significantly associated with older melanoma patients (OR = 6.075, 95CI = 2.013-18.333 dan OR = 13.263, 95CI = 1.518-115.901, respectively). BRAF mutations were associated with lower overall survival (Median survivals were 16.5 vs 31.4 months, Log-rank test P=0.001). NRAS mutations were not significantly associated with lower overall survival. Conclusion: In this study, melanoma patients are largely diagnosed at the late stages with ulceration and involvement of regional lymph nodes. BRAF mutations are associated with lower survival of cutaneous melanoma patients. © 2024 Elsevier B.V., All rights reserved.