Molecular determinants of resistance. (A) Copy number alterations, translocations, and driver mutations in MM in 6 patients with available WGS and RNA sequencing are indicated at baseline (T1) and at relapse (T2). Cancer clonal fractions (CCF) with enrichment of a KRAS mutation at T2 in responding patient P6 (B) (patients P10 and P12 are shown in supplemental Figure 3), in contrast with presence of an NRAS mutation shared between T1 and T2 in a nonresponding patient (patient P3) (C). (D) BRAF expression in MM cells decreased at T2 compared with T1 in most patients, with the notable exception of patient P4 who showed a fivefold increase. (E) Patient P4 harbored an acquired translocation within the BRAF gene.