Efficacy and tolerance of BRAF and MEK inhibitors on metastatic melanoma carrying the orphan pV600_K601 delinsE mutation of the BRAF gene.

Dear Editor, Approximately 50% of cutaneous melanomas carry mutations in the I BRAF i gene, most frequently located at exon 15, codon 600, and resulting in constitutive BRAF-mediated activation of the mitogen-activated protein kinase (MAPK) pathway.1 BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) have been approved for the treatment of metastatic melanomas with activating BRAF p.V600E or p.V600K mutations which account for 90% of BRAF-mutated melanomas.1,2 Although efficacy of BRAFi/MEKi have been reported with other activating mutations located at codon 600 (V600R, V600D),2,3 their relevance in the setting of "orphan" non-p.V600E/K/R/D mutations of uncertain significance has seldom been reported.2 We report the efficacy of BRAFi/MEKi in a metastatic melanoma with a mutation combining the deletion of the valine (V) at position 600, the deletion of the lysine (K) at position 601, and insertion of a glutamic acid (E). Efficacy and tolerance of BRAF and MEK inhibitors on metastatic melanoma carrying the orphan pV600 K601 delinsE mutation of the BRAF gene High Resolution Melting for rapid screening on the primary melanoma was consistent with a mutation of the I BRAF i gene in exon 15, but pyrosequencing did not detect mutations in codon 600. [Extracted from the article]