Constitutive activation of NOTCH1 in the intestinal epithelium of mice, harbouring KRASG12D activation and p53 deficiency (VilCreERKrasG12D/+p53fl/flRosa26N1icd/+ ; KPN), generated highly invasive, poorly differentiated, serrated intestinal adenocarcinomas that readily metastasize to the liver and recapitulate the poor-prognosis CMS4 and CRIS-B subtypes of human CRC [384]. The gene discussed is NOTCH1; the disease is colorectal carcinoma.