Fig. 3. Copy number loss as a potential resistance mechanism in an independent cohort.

(A) Boxplots summarize burden of copy number gain or loss in three patient subgroups from the Van Allen cohort: clinical benefit, long-term survival with no clinical benefit, and minimal or no clinical benefit; median values (lines) and interquartile range (whiskers) are indicated. P values were calculated using a two-sided Mann-Whitney U test (P = 0.016 for burden of copy number loss in clinical benefit vs. minimal or no clinical benefit, and P > 0.05 for all others). (B) Gene set enrichment analysis (GSEA) results show top enriched KEGG pathways from down-regulated genes (blue bars) and up-regulated genes (red bars) in high burden of copy number loss group versus low burden of copy number loss group (FDR-adjusted P < 0.001). (C) Proportions of patients with clinical benefit, long-term survival with no clinical benefit, and minimal or no clinical benefit were calculated within each of the four patient subgroups: high mutational load and low burden of copy number loss, high mutational load and high burden of copy number loss, low mutational load and low burden of copy number loss, and low mutational load and high burden of copy number loss. The numbers in parentheses indicate the number of patients with different levels of response (clinical benefit, long-term survival, and no clinical benefit) out of the total number of patients in each of the four patient subgroups.