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Canadian Journal of Gastroenterology and Hepatology
Volume 2018, Article ID 6152928, 7 pages
Research Article

Microsatellite Instability in Mouse Models of Colorectal Cancer

1The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia
2ACT Pathology, The Canberra Hospital and Australian National University Medical School, Canberra, ACT, Australia
3St. Vincent’s Clinical School, UNSW Medicine, UNSW Sydney, Sydney, NSW, Australia
4School of Medicine, Western Sydney University, Campbelltown, NSW, Australia

Correspondence should be addressed to Maija R. J. Kohonen-Corish; ua.gro.navrag@hsiroc.m

Received 2 November 2017; Revised 20 January 2018; Accepted 29 January 2018; Published 1 March 2018

Academic Editor: Ashok Kumar

Copyright © 2018 Nicola Currey et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Microsatellite instability (MSI) is caused by DNA mismatch repair deficiency and is an important prognostic and predictive biomarker in colorectal cancer but relatively few studies have exploited mouse models in the study of its clinical utility. Furthermore, most previous studies have looked at MSI in the small intestine rather than the colon of mismatch repair deficient Msh2-knockout (KO) mice. Here we compared Msh2-KO, p53-KO, and wild type (WT) mice that were treated with the carcinogen azoxymethane (AOM) and the nonsteroidal anti-inflammatory drug sulindac or received no treatment. The induced tumors and normal tissue specimens from the colon were analysed with a panel of five mononucleotide repeat markers. MSI was detected throughout the normal colon in untreated Msh2-KO mice and this involved contraction of the repeat sequences compared to WT. The markers with longer mononucleotide repeats (37–59) were the most sensitive for MSI while the markers with shorter repeats (24) showed only minor change. AOM exposure caused further contraction of the Bat37 and Bat59 repeats in the distal colon of Msh2-KO mice which was reversed by sulindac. Thus AOM-induced carcinogenesis is associated with increased instability of mononucleotide repeats in the colon of Msh2-KO mice but not in WT or p53-KO mice. Chemoprevention of these tumors by sulindac treatment reversed or prevented the increased MSI.