FIG 3.

Mutation analysis identifies known and novel acquired resistance patterns in patients treated with anti-EGFR antibodies. (A) Scatter plot depicting the difference in percentage (baseline ctDNA frequency minus archival tissue frequency) of patients bearing a mutation in each gene, for anti-EGFR (y-axis) and non–anti-EGFR (x-axis) groups. Genes with relatively higher frequency of mutation in the anti-EGFR group are labeled. (B) Bar plot showing Benjamini-Hochberg-adjusted P values (–log₁₀ transformed) from Fisher's exact tests for differences in mutation frequency between time points in anti-EGFR (red) and non–anti-EGFR (green) groups. Dotted lines indicate adjusted P = .05. For each gene shown, significant increases in mutation frequency post-treatment are unique to the anti-EGFR group. (C) Detailed analysis of genes of interest. First row (bar plots) indicates frequency (percentage of patients) of variant types at archival tissue (A) and baseline ctDNA (B) time points for each treatment group (anti-EGFR ±). The second row (bar plots) indicates the number of patients bearing multiple variants in the same gene. Third row (boxplots) indicates rVAF of mutations in each group and are compared with Wilcoxon mean rank-sum P values. ctDNA, circulating tumor DNA; EGFR, epidermal growth factor receptor; rVAF, relative variant allele fraction; SNV, single-nucleotide variant.