Mutations in tumour suppressor genes (APC, SMAD4 and TP53) and oncogenes (KRAS and PI3KCA) were introduced using the CRISPR-Cas9 system into organoids derived from normal intestinal epithelium. Organoids with all five mutations grew independently of in vitro growth factors and formed tumours in mice, but did not metastasize to the liver after injection into mouse spleens. Mutations introduced into organoids derived from chromosome-instable adenomas did form macrometastatic colonies.
References
Matano, P. et al. Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat. Med. 10.1038/nm.3802
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Engineering carcinogenesis in intestinal organoids. Nat Rev Gastroenterol Hepatol 12, 188 (2015). https://doi.org/10.1038/nrgastro.2015.40
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DOI: https://doi.org/10.1038/nrgastro.2015.40
