Lack of BRAF V600E mutation in human myeloma cell lines established from myeloma patients with extramedullary disease

Abstract

After whole genome sequencing of samples from 38 patients with multiple myeloma (MM) had identified one patient with an activating mutation of BRAF (G469A), BRAF mutations have been intensively screened in MM patients.1 Among 161 samples, 3 K601N and 4 V600E (the most common in melanoma) mutations were found in 4% of the patients.1 This low incidence is still consistent with a recent study involving 32 MM samples that reported no BRAF mutation.2 In the more specific field of extramedullary disease (EMD) in MM, Andrulis et al.3 recently reported a significant association with BRAF exon 15 mutations. Notably, the V600E mutation was found in 8.5% of patients with EMD (4 out of 47) versus 1.5% of patients without EMD (3 out of 204). The EMD of the four patients harbouring BRAF V600E mutation (all soft tissue plasmacytomas) was primitive for one patient and secondary after one or several lines of treatments for the three others. This recent work contrasts with an older one in which no BRAF mutation was found in 65 fresh bone marrow samples from 18 patients with PCL and 47 patients with MM at diagnosis.4 The incidence of EMD in MM is rare at diagnosis but extramedullary involvement increases with disease evolution. Spreading of MM cells out of the bone marrow is commonly associated with a poor outcome and resistance to salvage therapies.5 In this context, the recent findings of Andrulis et al. raise the interest of identifying patients with EMD carrying the BRAF V600E mutation, who could benefit from the V600E-mutated BRAF protein targeted therapy, that is, vemurafenib.