Figure 4

TP53 functions as a cancer functional genomic complexity (FGC) driver. (A) (Top panel) Z-scores for FGC, CIN, and tFA in each HCC sample are plotted in each barplot in the FGC ranked order. (Bottom panel) The mutation frequency for 26 genes, mutated in more than 3 samples of Thai HCC, was shown (right panel). The occurrence of mutation of regarding gene in each sample and mutation types were indicated in different colors. Samples were represented in columns in the same order of top panel. (B) (Top panel) TP53 mutations sites among Thai HCC were shown. Transactivation motif (TAD; 6–29), DNA binding motif (DBD; 95–288), and tetramerization motif (Tetramer; 318–358) were depicted in a different colored box; green, orange, and navy, respectively. Green or black dots indicate missense or truncating mutation, respectively. (Bottom panel) The top plot indicates the FGC score of each sample in the rank order. TP53 mutation incidence in each sample was plotted in black according to the mutation sites. Mutation sites of TP53 depending on DNA binding domain (DBD) and out of DBD (O-DBD) were plotted separately. (C–E) KM survival analysis based on TP53 mutation status in the Thai HCC (C), Thai iCCA (D), and TCGA HCC (E) patients. (F) The proportion of occurrence of TP53 mutation in HFGC and LFGC of TIGER-LC, Thai HCC, iCCA, TCGA HCC were shown. H or L indicates HFGC and LFGC, respectively. Significant enrichment of TP53 mutation was marked with red star based on the Fisher’s exact test (p-value < 0.05). (G,H) The CIN (G) and FGC (H) level between TP53 WT and TP53 mutation among Thai HCC. P-values based on the Welch two-sample t-test were depicted. NSYN, non-synonymous mutation; FS, frameshift mutation; SS, splice site mutation; NS, nonsense mutation; SSA, splice site acceptor.