Epigenetic regulation takes a significant role in the initiation and progression of CRC.[22] In our cohort, various genes related to the epigenome were mutated at a high rate, such as ARID1A, KMT2C, KMT2D, and KDM6A, which are commonly altered in CRC.[23] Overall, the mutational spectrums identified in our PDOs and PDCs reflected the genomic features of their parental tumors (Figure 2A; Table S2A,B, Supporting Information). This evidence concerns the gene ARID1A and colorectal carcinoma.