...the impact of preexisting MEK1P124 alterations on clinical response of BRAFV600-mutant metastatic melanoma to BRAF inhibitor therapy. Pretreatment MEK1P124 mutations were found in 12 of 123 (10%) tumor biopsies in four published cohorts (Table 1). Four tumors carried non-P124 MEK1 mutations (Table 1). The presence of a preexisting MEK1P124Q/S mutation was associated with fewer RECIST responses (complete response + partial response) and a shorter PFS compared with patients who had MEK1P124–wild-type tumors (response rate 33% vs. 72%, P = 0.018; median PFS 3.1 vs. 4.8 months, HR, 2.46 [95% confidence interval (CI), 1.32–4.56; P = 0.004.