We sought to better delineate the molecular diversity of CRC by determining mutational signatures that reflect different mutational processes, such as spontaneous deamination of 5-methylcytosine (signature 1), defective DNA MMR (signatures 6, 15, and 20), recurrent POLE somatic mutations (signature 10), and tobacco chewing habits (signature 29). The gene discussed is POLE; the disease is colorectal carcinoma.