BRAF-mutated melanoma

Approximately one-half of advanced (unresectable or metastatic) melanomas harbor a mutation in the BRAF gene, with V600E being the most common mutation.

Targeted therapy with BRAF and MEK inhibitors is associated with significant long-term treatment benefit in patients with BRAF V600-mutated melanoma. Therefore, molecular testing for BRAF mutations is a priority in determining the course of therapy.

Numerous BRAF testing methods were identified, including DNA-based companion diagnostic tests and DNA- and protein-based laboratory-developed tests.

Molecular profiling has shown that mutation load increases with melanoma tumor progression and that unique patterns of genetic changes and evolutionary trajectories for different melanoma subtypes can occur.

Discordance in the BRAF mutational status between primary and metastatic lesions, as well as intratumoral heterogeneity, is known to occur.

Additionally, the development of acquired resistance to combination BRAF and MEK inhibitor therapy is still a formidable obstacle.

Therefore, tumor heterogeneity and the development of acquired resistance have important implications for molecular testing and ultimately the treatment of patients with advanced-stage melanoma.

Open references

 Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine. Cheng L, Lopez-Beltran A, Massari F, MacLennan GT, Montironi R. Mod Pathol. 2018 Jan;31(1):24-38. doi : 10.1038/modpathol.2017.104 PMID: 29148538 Free