Fig. 3.

Temporal evolution and trajectory of MAPK alterations. A Clusters of subclonal mutations sampled over time with the mutational VAF represented as a percentage on the y axis show the trajectory of the subclone harboring the BRAF V600E mutation over time in response to treatment and the later emergence of a subclonal KRAS Q61R mutation after the end of triple MAPK inhibition. B A reconstructed phylogenetic tree of subclones across all time points shows that the BRAF V600E is subclonal and ancestral to the clone that gives rise to a KRAS Q61R mutation. C RNA expression shows an increase in MAPK pathway activation, measured as a combined z-score, over time in response to treatment with triple MAPK inhibition therapy