APC and adenoma: These are: (1) CMS1 (associated with microsatellite instability and upregulation of immune genes, 14%); (2) CMS2 (defined by the canonical ‘adenoma-carcinoma sequence’ with mutations in adenomatous polyposis coli (APC), p53, and RAS, 37%); (3) CMS3 (associated with metabolic dysregulation, i.e. increased glutaminolysis and lipidogenesis, 13%); and (4) CMS4 (associated with epithelial–mesenchymal transition, 23%) [23].