Genetic instability in MMR-deficient CRC. (A) Pie chart represents the portion of R (light blue) and NR (dark blue) sequences. Bar plots represent the distribution of the 5 genomic region types (3’ UTR, coding exonic, intronic, 5’ UTR) captured by WES in R (light blue) and NR (dark blue) sequences. (B) Bar plot of the number of mutations per captured megabase (Nb mutations/Mb) across the whole exome for 47 MSI tumors in R sequences (light blue) and in NR sequences (dark blue). The median mutation rate in all types of CRC was described previously25 and is indicated by the red dotted line. The heatmap below shows the percentage of mutated genes in coding R and NR sequences. (C) Box plots show the number of mutations per megabase (log10 scale) in all types of CRCs from the TCGA colon adenocarcinoma data set (red), in MSI CRC within R sequences (light blue), and in MSI CRC within NR sequences (dark blue). Grey dots indicate the mutation frequencies for each MSI tumor. The results of the t test between groups were as follows: ***P < .001. (D) Bar plot of the percentage of genes with different mutation frequencies for MSI (blue) and microsatellite stable (MSS) (red) CRCs. (E) Box plots represent the number of mutations per megabase for 3 genomic regions (UTRs, coding exonic, intronic). Grey dots represent the value for individual tumors (n = 47). The results of the t test between groups were as follows: ***P < .001. (F) The mutation frequencies of 3 gene regions (UTRs, coding exonic, intronic) are shown, where grey dots represent each individual mutation in NR (left) and R (right) sequences. Mutation frequencies in R sequences are shown according to the microsatellite length and nucleotide composition (colored dots and lines). IHC, immunohistochemistry.