Two Case Reports of Rare BRAF Mutations in Exon 11 and Exon 15 with Discussion of Potential Treatment Options.

BRAF mutations occur in up to 50% of melanomas. Mutations in the BRAF gene directly influence the patient's treatment because several inhibitors are available that only target BRAF ^V600 mutations. Herein, we describe two cases of patients with metastatic melanomas, each carrying a 'nonstandard' mutation in the BRAF gene: BRAF ^K601E and BRAF ^G466E , respectively. The first patient was treated with a MEK inhibitor and the second one with ipilimumab. However, not all BRAF mutations result in increased BRAF kinase activity, and clinical data for 'nonstandard' mutations, such as those described in our case report, are sparse. Therefore, treatment with MEK inhibitors can be helpful in cases where BRAF mutations result in increased activity, whereas immune checkpoint inhibitors might be used in cases where the mutations lead to activity levels below those of the wild type.