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Background  Mutations in the activation segment of the v-raf murine sarcoma viral oncogene homolog B ( BRAF)  gene are present in approximately 50% of melanomas. The selective BRAF inhibitor vemurafenib has demonstrated significant clinical benefits in patients with melanomas harboring the most common mutations (V600E, V600K and V600R). However, the clinical activity of BRAF inhibitors in patients with rare mutations of codon 600 and the surrounding codons has not been documented.    Case presentation  We used the BRAF inhibitor vemurafenib to treat a patient presenting a rare p.V600_K601delinsD-mutated melanoma. An objective response was evidenced by two months of progression-free survival. By cloning and sequencing  BRAF  exon 15, we confirmed that a dual mutation was present on a single allele and thus resulted in a  BRAF   V600DK601del   mutant protein. We also performed an  in silico  crystal structure analysis of the mutated protein, in order to characterize the nature of the putative interaction between vemurafenib and the mutant protein.    Conclusion  This clinical experience suggests that (i) patients with  BRAF   V600DK601del  -mutation-positive melanoma can be treated successfully with the oral BRAF inhibitor vemurafenib and (ii) molecular screening in this context should encompass rare and complex mutations.

The clinical response to vemurafenib in a patient with a rare BRAF V600DK601del mutation-positive melanoma