TP53 and colitis: The presence of immunosuppressive cytokines such as IL-23 and IL-17 links CMS4 cancers to colitis-associated colorectal carcinoma, where TP53 inactivation occurs early in the transformation to dysplasia [49], which is distinct from CMS2 precursor lesions, where the loss of the TP53 tumor suppressor function occurs late in the adenoma-to-carcinoma sequence.