Fig. 1: Mutation profiling of 2105 colorectal tumors.

a Tumors are sorted based on the number of mutations with each dot indicating mutations in that tumor. Jitter was added to easier visualize overlapping data points. The vertical dotted line separates hypermutated and non-hypermutated tumors (see “Methods”). Tumors with MSI and POLE exonuclease domain mutations are frequent in hypermutated tumors. b Analysis of hypermutated tumors. Tumors with mutations in DNA mismatch repair genes (MMR: MLH1, MLH3, MSH2, MSH6, or PMS2), tumors with non-silent non-truncating mutations in POLE, and their MSI status are shown. c MSI or MSS tumors were examined for the impact of POLE exonuclease non-silent non-truncating mutations on overall mutation burden. The boxplots show tumors with and without POLE exonuclease (exo) domain mutations and the MSI status. The center line, bounds, and whiskers of the boxplots are median, first and third quartiles, and outliers, respectively. The medians for boxes without overlapping notches are significantly different at the 0.95 confidence level. MSS tumors with mutations in the POLE exonuclease domain have significantly higher mutation burden compared to the MSS and MSI tumors without the POLE exonuclease domain mutations.