Journal article
Genetic editing of colonic organoids provides a molecularly distinct and orthotopic preclinical model of serrated carcinogenesis
TRM Lannagan, YK Lee, T Wang, J Roper, ML Bettington, L Fennell, L Vrbanac, L Jonavicius, R Somashekar, K Gieniec, M Yang, JQ Ng, N Suzuki, M Ichinose, JA Wright, H Kobayashi, TL Putoczki, Y Hayakawa, SJ Leedham, HE Abud Show all
Gut | BMJ PUBLISHING GROUP | Published : 2019
Abstract
Objective Serrated colorectal cancer (CRC) accounts for approximately 25% of cases and includes tumours that are among the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen-Activated kinase pathway gene, BRAF, and epigenetic modifications termed the CpG Island Methylator Phenotype, leading to epigenetic silencing of key tumour suppressor genes. It is still not clear which (epi-)genetic changes are most important in neoplastic progression and we begin to address this knowledge gap herein. Design We use organoid culture combined with CRISPR/Cas9 genome engineering to sequentially introduce genetic alterations associated wi..
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Awarded by V Foundation for Cancer Research
Funding Acknowledgements
This work was supported by Cure Cancer Australia/Cancer Australia (APP1102534), the Cancer Council SA Beat Cancer Project on behalf of its donors and the State Government of South Australia through the Department of Health SA, by Pathology Queensland, by the Australian National Health and Medical Research Council (NHMRC) (through APP1081852, APP1140236), by the National Institutes of Health (NIH) (K08 CA198002, R00 AG 045144, R01 CA211184), the Department of Defense (CA120198), the V Foundation V Scholar Award, the Sidney Kimmel Scholar Award, the Pew-Stewart Trust Scholar Award, the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund, the American Federation of Aging Research, as well as by the Koch Institute Support Grant P30-CA14051 from the National Cancer Institute. DLW is supported by a NHMRC Career Development Fellowship, VLJW by a Gastroenterological Society of Australia Senior Research Fellowship.