Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2016; 22(2): 815-822
Published online Jan 14, 2016. doi: 10.3748/wjg.v22.i2.815
Mouse models for the discovery of colorectal cancer driver genes
Christopher R Clark, Timothy K Starr
Christopher R Clark, Timothy K Starr, Department of Obstetrics, Gynecology and Women’s Health, University of Minnesota, Minneapolis, MN 55455, United States
Author contributions: Clark CR performed the literature search, wrote the first draft and approved of the final version; and Starr TK edited and approved of the final manuscript.
Supported by 3M Science and Technology Fellowship Award (to Clark CR); National Cancer Institute of the National Institutes of Health, No. 5R00CA151672-03 (to Star TK).
Conflict-of-interest statement: The authors declare no conflict of interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Timothy K Starr, PhD, Assistant Professor, Department of Obstetrics, Gynecology and Women’s Health, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, United States. star0044@umn.edu
Telephone: +1-612-6254425 Fax: +1-612-6254425
Received: May 20, 2015
Peer-review started: May 20, 2015
First decision: August 26, 2015
Revised: September 9, 2015
Accepted: November 24, 2015
Article in press: November 24, 2015
Published online: January 14, 2016
Processing time: 231 Days and 15.2 Hours
Abstract

Colorectal cancer (CRC) constitutes a major public health problem as the third most commonly diagnosed and third most lethal malignancy worldwide. The prevalence and the physical accessibility to colorectal tumors have made CRC an ideal model for the study of tumor genetics. Early research efforts using patient derived CRC samples led to the discovery of several highly penetrant mutations (e.g., APC, KRAS, MMR genes) in both hereditary and sporadic CRC tumors. This knowledge has enabled researchers to develop genetically engineered and chemically induced tumor models of CRC, both of which have had a substantial impact on our understanding of the molecular basis of CRC. Despite these advances, the morbidity and mortality of CRC remains a cause for concern and highlight the need to uncover novel genetic drivers of CRC. This review focuses on mouse models of CRC with particular emphasis on a newly developed cancer gene discovery tool, the Sleeping Beauty transposon-based mutagenesis model of CRC.

Keywords: Mouse models, Colorectal cancer, Cancer genes, Insertional mutagenesis, Transposable elements

Core tip: Successful implementation of targeted therapy will require a much more sophisticated understanding of colorectal cancer genetics, including the ability to discern “driver” mutations from the more common “passenger” mutations. Interpreting causality from large human genomic datasets will benefit from data produced by animal models and will expedite clinical trials using targeted therapies. This review describes the benefits and limitations of both traditional and new mouse models that are being used to discover and define colorectal cancer driver genes.