(A) Z-scores of median gene expression of (i) all genes, (ii) HSP90, (iii) Chaperonins, and (iv) the Proteasome averaged across tumors stratified by the total number of copy number alterations (CNAs). Expression of HSP90, Chaperonins, and Proteasome gene sets increases with the mutational burden of tumors (weighted R2 of 0.81, 0.87, and 0.86, respectively). Error bars are 95% confidence intervals determined by bootstrap sampling. (B) Correlation coefficients (r) of the expression of each gene in the genome (gray) in tumors stratified by the total number of substitutions. Shown in arrows are the correlation coefficients for HSP90 (blue), Chaperonins (orange), and the Proteasome (purple). Dashed lines in intervals of 0.25 are for viewing purposes only. (C) Median correlation coefficients of 10 million randomly sampled gene sets of the same size as HSP90, Chaperonins, and the Proteasome (n=28) in gray. Red line denotes the median correlation coefficients of genes in HSP90, Chaperonins, and the Proteasome (0.66). (D–E) Log-scale heatmap of changes in the Z-scores of median gene expression values of gene sets in for tumors stratified by the total number of substitutions (D) or CNAs (E) for cancer subtypes in TCGA. Changes in the mean gene expression of all genes, HSP90, Chaperonins, and Proteasome gene sets in the lowest and highest mutational burden bin for each cancer subtype are shown. Colors denote whether changes in gene expression from low mutational burden bins to high mutational burden bins are positive (green) or negative (red). Expression of HSP90, Chaperonins, and Proteasome gene sets increases with the mutational burden of tumors across cancer types stratified by the number of somatic nucleotide variants (SNVs) (p<0.05, p<1.3 × 10–4, p<5.2 × 10–4, respectively; Wilcoxon signed-rank test) and CNAs (p>0.05, p<9.3 × 10–3, p<1.9 × 10–2 respectively; Wilcoxon signed-rank test).