CTNNB1 and neoplasm: To evaluate whether these RNF43 hot-spot frameshift mutations functionally contribute to tumor progression, we selected several CRC cell lines with wildtype RNF43 and CTNNB1 and either wildtype or mutant APC20, namely C10 (APCWT), LS513 (APCWT) and HT29 (APCmut) and utilized CRISPR-Cas9 to genetically edit the target sites of RNF43-117aa (RNF43117mut) and RNF43-659aa (RNF43659mut) (Supplementary Fig. 1a).