Hino H, et al. - In order to determine the clinicopathological and mutation profiles of colorectal cancer (CRC) with POLE (DNA polymerase epsilon) mutations, researchers used 910 surgically resected primary CRCs in this study on which whole-exome sequencing was performed. Two groups were formed: hypermutators, defined as tumors exceeding 500 counts of nonsynonymous single nucleotide variants (SNVs), and nonhypermutators consisted of the remaining. Common-hypermutators group consisted of 57 (6.3%) tumors and POLE category tumors were 10 (1.1%). A significantly higher SNV count was seen in POLE category tumors as compared to common-hypermutators. They found the association of all POLE category tumors with exonuclease domain mutations, such as P286R, F367C, V411L, and S297Y, in the POLE gene. Compared to those with nonhypermutators and common-hypermutators, patients with POLE category tumors were significantly younger. Overall, they concluded that the features of CRCs with POLE proofreading deficiency were different from those of other CRCs. For personalized management of CRCs, the possible clinical significance of the analysis of POLE proofreading deficiency was suggested.