Nikolaev and colleagues examined early CRC carcinogenesis, and their seminal work using whole-exome sequencing of 24 colorectal adenomas demonstrated that these pre-cancers exhibited a ‘mutator phenotype’ of high, single nucleotide substitutions compared to non-transformed cells, which was enabled through inactivation of a gene responsible for genomic stability, proposed to be APC [21]. Here, APC is linked to colorectal carcinoma.