In a previous large-scale genomic study of human colorectal samples three subtypes of colorectal cancer were identified22: (1) microsatellite stable tumors (MSS), (2) tumors with MSI due to a DNA MMR system deficiency, and (3) hypermutated tumors that harbor mutations in the exonuclease (proofreading) domain of the DNA polymerases Pol δ (POLD1) and Pol ε (POLE). The gene discussed is POLE; the disease is colorectal cancer.