Routine sequencing of BRAF exon 15 improves therapeutic stratification for metastatic melanoma

Objective BRAF V600E/K mutations are significant drivers of metastatic melanoma, and therapies that selectively target these mutations have significantly improved patient long-term survival. Emerging evidence suggests that tumors harboring BRAF non-V600E/K mutations are susceptible to MEK-targeting therapies, but these mutations are not always assessed in clinical workup. To assess whether patient stratification for targeted therapy can be improved, we characterized the prevalence and nature of BRAF non-V600E/K mutations in a cohort of patients diagnosed with metastatic melanoma. Methods We extracted DNA from 99 specimens collected between June 2019 and September 2021. The samples were analyzed using next-generation sequencing to identify mutations in BRAF exon 15 and to assess their susceptibility to targeted therapies. Results Eleven percent of patient specimens contained BRAF non-V600E/K mutations in exon 15. Of the mutations identified, all have prior evidence of susceptibility to targeted MEK therapies. Among those patients, less than half received targeted MEK therapies. Conclusions Next-generation sequencing is a sensitive platform for profiling BRAF exon 15 mutations that cannot be detected by other techniques. Our results support the routine sequencing of BRAF exon 15 to improve patient stratification for therapy.