Deep genomic characterization of the extramedullary lesion prompted a personalized therapeutic approach.Acquisition of <i>CIC</i> mutation confers a mechanism of BRAF-MEK inhibitor drug resistance in multiple myeloma.The in silico interrogation of the CoMMpass clinical study revealed 10 patients with somatic mutations of <i>CIC</i> and its downregulation at gene expression level in multiple myeloma.
We found a significant enrichment of RAS/BRAF mutations in rrMM compared to NDMM (P=0.011), which was mainly due to an increase of NRAS mutations (P=0.010).
The spectrum of KRAS, NRAS, and BRAF codon mutations varied across subgroups with NRAS mutations at Q61 codon being common in hyperdiploid (HRD) and t(11;14) myeloma while being rare in MMSET and MAF.
Our data confirm and extend previous published evidence that MAPK pathway activation is recurrent in myeloma; the finding that it is mediated by BRAF mutations in a significant fraction of patients has potentially immediate clinical implications.
Multiple myeloma (MM) was characterized by frequent mutations in KRAS/NRAS/BRAF within the EGFR pathway that could induce resistance to EGFR inhibitors.
Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials.