Overall, 16% of CRCs are hypermutated, and most of these fall into the category of tumors with microsatellite instability (MSI), which is either due to mutations in the MMR or promoter methylation of the MLH1 gene (CIMP).15,16 By contrast, the majority of CRC tumors have markedly fewer mutations but exhibit chromosomal instability (CIN), which is primarily caused by hereditary or spontaneous inactivating mutations in the APC gene. Here, APC is linked to colorectal carcinoma.