APC and adenoma: Sievers has investigated the mutational spectrum of small colorectal polyps and has shown that: small polyps can have multiple driver pathogenic mutations—67% APC mutations, 15% KRAS mutations, 8% TP53 mutations, 10% FBXW7 10% mutations and 17% BRAF mutations (SSAs and HPs)—small polyps can have multiple driver mutations—31% of these tumors display multiple pathogenic mutations—adenomas contain subpopulations at lower allelic frequencies—private mutations—and statistical inferences predict that detectable intratumoral heterogeneity is an event occurring early during adenoma development [211].