In addition to demonstrating mutational signatures consistent with dMMR, a study in LS patients revealed mutations in APC, KRAS and other established cancer drivers in 20% of the crypts or glands from morphologically normal gut epithelium and a single morphologically normal crypt with dMMR.Further similar studies are required to provide a comprehensive picture of early colorectal carcinogenesis in FAP and LS. The gene discussed is APC; the disease is Familial adenomatous polyposis.