Extended Data Fig. 6: Exon 20 loop insertions are a distinct class of EGFR mutations. | Nature

Extended Data Fig. 6: Exon 20 loop insertions are a distinct class of EGFR mutations.

From: Structure-based classification predicts drug response in EGFR-mutant NSCLC

Extended Data Fig. 6

a, Dot plot of mutant/WT IC50 values of Ba/F3 cells expressing exon 20 loop insertion mutations and treated with indicated classes of EGFR TKIs. Dots are representative of average of n=3 replicate mutant/WT IC50 values of individual cell lines expressing exon 20 insertion mutations with individual drugs. Bars are representative of average mutant/WT IC50 values ± SEM for each class of EGFR TKI and all Ba/F3 cell lines. p-values were determined by one-way ANOVA with unequal SD as determined by Brown-Forsythe test to determine differences in SD. Holm-Sidak’s multiple comparisons test was used to determine differences between groups. b, Tumor growth curves for PDXs harboring EGFR S768dupSVD exon 20 insertion mutation treated with indicated inhibitors. Tumors were measured three times per week and symbols are average of tumor volumes ± SEM. Mice were randomized into four groups: vehicle (N=4), poziotinib 2.5mg/kg (N=5), osimertinib 5mg/kg (N=4), and osimertinib 25mg/kg (N=5) . Mice received drug 5 days per week, and mice were euthanized at day 21 to harvest tumors. c, Dot plot of percent change in tumor volume on day 21 of tumors described in panel c (vehicle, N=4 mice, poziotinib 2.5mg/kg, N=5 mice, osimertinib 5mg/kg, N=4 mice, and osimertinib 25mg/kg, N=5 mice). Dots are representative of each tumor, and bars are representative of average ± SEM for each group. Statistical differences were determined by ordinary one-way ANOVA with post-hoc Tukey’s multiple comparisons test to determined differences between groups. d, Heat map with unsupervised hierarchical clustering of log (Mutant/WT) ratios from Ba/F3 cells expressing indicated exon 20 loop insertions after 72 h of indicated drug treatment. Squares are representative of the median of n=3 replicates. e, Bar plot of average mutant/WT ratio of Ba/F3 cells expressing exon 20 loop insertions separated by mutational groups for indicated drug classes. Bars are representative of average mutant/WT ratio for all mutations and drugs in the indicated groups, dots are representative of average (n=3) mutant/WT ratio of individual mutations and drugs. Error bars are representative of SEM for each bar. Statistical differences between near- and far-loop mutants was determined by two-sided unpaired t-test with unequal variance

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