Fig. 6
Multi-omic molecular alterations in the pan-cancer CS subgroups. (A) Heatmaps showing common alterations in somatic mutations, cancer driver genes, and copy number amplification or deletion in pan-cancer samples according to the CS subgroups. (B) Circular plots displaying the differences in single nucleotide polymorphism (SNP) and copy number variation (CNV) among the CS subgroups. (C) Tumor mutation burden (TMB), CNV burden, homologous recombination (HR), loss of heterozygosity (LOH), base excision repair (BER), and nucleotide excision repair (NER) levels in the CS subgroups. (D) Expression of transcription factors in the CS subgroups. (E) Heatmap of alteration frequencies in CS-related cancer driver genes. Color bars showed the proportions of alteration types for each gene (right panel) or cancer subtype (top panel). (F) Expression and regulation of cancer driver genes in the CS subgroups. From left to right: malignant degree (importance for tumor growth); mRNA expression (median normalized expression levels); expression vs. methylation (correlation between mRNA expression and DNA methylation β-value); amplification frequency (difference in copy number amplification fraction of a driver gene between subgroup samples and all samples); and deletion frequency (difference in copy number deletion fraction). (G) Histogram of CNV frequencies of driver genes in each cancer type. (H) Correlations of transcriptional expression with CNV and DNA methylation for driver genes in different cancer types. (I) Protein structures of driver genes common to the C1 and C2 subgroups. PEG3 and FAM153B mutations were clustered in protein functional domains. Color spheres represented mutations classified by mutation frequency. (J) Structure-based calculations of the effect of driver gene mutations on protein folding energy (ΔΔGfold).
