Genetic alterations in MMR‐associated pathways are concomitant with the hypermutated phenotype.[21] The derivatives of two microsatellite instability‐high (MSI‐H) patients (SNU‐4376A and SNU‐4398) harbored missense mutations in the POLE gene, with SNU‐4398 having an additional point mutation in MSH3, in concordance with their classification as hypermutated CRC.[22] The majority of CRC cases harbored activating mutations in CTNNB1 or inactivating mutations in APC, AXIN2, FBXW7, or FAM123B. This evidence concerns the gene POLE and colorectal carcinoma.