Next generation sequencing for personalized therapy: About a class III BRAF N581K mutation associated to NRAS Q61L mutation in malignant melanoma: Case report

In metastatic stage, therapeutic approach for malignant melanoma is particularly based on performance status, metastatic sites, and BRAF V600 status (BRAF V600E/V600K or V600R (class I BRAF mutations). In most cases, BRAF mutations and NRAS mutations are mutually exclusive to each other. However, some rare BRAF mutations class III are preferentially associated with a NRAS mutation, leading to the MAP Kinase pathway activation and subsequent cell proliferation. Melanomas with this double mutation are rare and difficult to treat because of the lack of codified therapeutic options. We report a patient with metastatic melanoma, harboring class III BRAF mutation (N581K) associated to NRAS mutation (Q61L) with treatment failure. He was treated in second line, after immunotherapy, by monotherapy of MEK inhibitor (MEKi), which underline the interest of NGS (Next Generation Sequencing) to early identify all mutations and enabling onco-dermatologist to discuss a treatment. Rare BRAF non V600 mutations represent 3 to 14% of melanoma mutants and the aim of this communication is to promote the next generation sequencing to extend the paradigm of individually therapeutic approach with target therapy into different spectrum of melanoma patients.