RNF43 and adenoma: Although the MSI pathway can sometimes give rise to serrated-type tumors, the CIMP adenoma-carcinoma pathway produces adenomas that resemble MSI carcinomas due to hypermethylation of MLH1 but lack the hallmark genetic disruption in APC; instead, tumors form in association with BRAF and KRAS mutations driven by an exclusive WNT activating RNF43 mutation in sporadic CRC (11, 12).