Ligand-dependent tumours are rich in mucins,49 reflected by the fact that RNF43 mutations are seen in 34.5% of genetic mutations responsible for mucinous adenocarcinoma, which are also more commonly associated with MSI.50,51 R-spondin gene fusion mutations lead to stromal overexpression and upregulation of the Wnt pathway in 10% of CRC.52 RSPO fusion mutations can induce ectopic crypt formation and are often documented genetic alterations arising from traditional serrated adenomas as well.53 This evidence concerns the gene RNF43 and neoplasm.