Mouse models for the discovery of colorectal cancer driver genes

World J Gastroenterol. 2016 Jan 14;22(2):815-22. doi: 10.3748/wjg.v22.i2.815.

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: Cancer genes; Colorectal cancer; Insertional mutagenesis; Mouse models; Transposable elements.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenomatous Polyposis Coli / genetics*
  • Adenomatous Polyposis Coli / metabolism
  • Adenomatous Polyposis Coli / pathology
  • Animals
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / metabolism
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Humans
  • Mice
  • Mutation*
  • Neoplasms, Experimental / genetics*
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Phenotype
  • Transposases / genetics
  • Transposases / metabolism

Substances

  • Biomarkers, Tumor
  • Transposases
  • sleeping beauty transposase, human