Using CRISPR gene editing, Matano et al. created CRC organoids with loss of function mutations in APC, SMAD4 and TP53, and gain-of-function mutations in KRAS and/or PIK3CA that grew independent from niche factors in vitro, and formed tumours after implantation under the kidney sub-capsule in mice [21]. Here, SMAD4 is linked to neoplasm.