Fig. 1

The landscape of genetic drivers in BRAF features distinct variants. a The size of the circle corresponds to the number of variants at that amino acid position. Variants that occupied a unique position are annotated. The vast majority of BRAF variants were found once in a single cancer type. b, c Secondary (non-V600) variant frequency peaks occur in residues that comprise the A-loop, the P-loop and residues critical for Mg⁺² chelation. The catalytic D576 (C-loop), which is in a cleft between the N- and C-lobes, is shown. d The relative proportion of the 10 most frequent variants in the four most common cancer types are shown. e Clock plot of BRAF signature score in BEAS-2B cells expressing vector control (ϕ), wild-type (WT) or 35 BRAF variants. Red and blue represents cells with the most and least BRAF activity, respectively. f BEAS-2B cells stably infected with vector alone (ϕ) or vector expressing BRAF alleles were injected into the flanks of NSG mice and monitored for growth. The association between the BRAF signature score and the time for tumor volume to reach 1 cm³ is shown in the inset. Tumor volume is expressed as the mean ± s.d. of at least six independent biological replicates