Defining the clinical characteristics of BRAF V600K melanoma mutations

Summary: Background: The BRAF V600K mutation is the second most common mutation in cutaneous melanoma, after V600E, and as a result, less is known about its defining characteristics. While both mutations lead to constitutive activation of the MAPK/ERK pathway, their clinical implications, including patient demographics, tumor characteristics, and treatment responses, differ.¹ Understanding these differences is crucial for optimizing patient management and therapeutic strategies. Methods: A set of 72 patients with V600K mutations and 46 patients with V600E were obtained and stratified by mutation type, age, gender, and stage of disease, with a particular emphasis on treatment modalities and outcomes. This study received institutional review board approval. Results: V600K mutations were more frequently observed in an older population than in V600E (66 vs. 57, p = 0.001). They also presented with advanced melanoma, with V600K patients more often presenting with metastasis compared to V600E (31% vs. 9%, p = 0.03). These patients required more aggressive treatment involving multiple agents with differing mechanisms of action, seen in 25% of cases compared to 6% in V600E (p = 0.03). Patients with V600K mutations were also often seen in a male population, more often found on the head and neck as compared to the trunk in V600E and often with a higher staging, although this data was not significantly significant. Extensive sun exposure was seen in both mutations. Discussion: V600K mutations are associated with an older, male population and advanced melanoma stages compared to V600E. This mutation may necessitate more complex treatment regimens potentially due alternative pathways taken by the mutation.¹ Our findings were limited by sample size and future directions include further histological comparison as well as the comparison of V600K mutations and other codon changes such as V600M, V600R, and V600G. References: 1. Nepote A, Avallone G, Ribero S, et al. Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma. <i>J Clin Med</i>. 2022;11(3):828. Shara Chopra¹, Sydney E. DeVore², Matthew Tsang¹, Arivarasan Karunamurthy¹ 1. Dermatology, UPMC, Pittsburgh, PA, United States. 2. School of Medicine, UPMC, Pittsburgh, PA, United States. Pigmentation, Melanoma, and Melanoma Immune Surveillance