This is notable since LS colorectal tumorigenesis is generally thought to follow the classic adenoma-carcinoma sequence, whereby MMRd is a late event in adenomas, with established Wnt signaling activation due to somatic APC, CTNNB1 or RNF43 PVs, that causes rapid progression to carcinoma [6,62]. The gene discussed is RNF43; the disease is carcinoma.