Consistent with previous clinical studies [39, 40], combinatorial genetic mutations of KrasG12D, p53, Apc, and Smad4 in healthy colonic organoids gave rise to adenocarcinoma organoids, while normal gastric and pancreatic organoids can be transformed into the adenocarcinoma organoids after p53 loss, KrasG12D expression or both [41]. The gene discussed is SMAD4; the disease is adenocarcinoma.