APC and colonic neoplasm: As Wnt-pathway activation is a key dependency for colon cancers, which in the majority cases occurs via inactivating mutations in APC, and in rare cases by activating mutations in CTNNB1 (β-catenin)31,32, we studied Wnt-independent growth properties of the proximal and distal organoids by introducing these mutations using CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 and single-guide RNAs (sgRNAs) targeting these genes (Fig. 1a).