Transposon mutagenesis identifies genes and evolutionary forces driving gastrointestinal tract tumor progression

Nat Genet. 2015 Feb;47(2):142-50. doi: 10.1038/ng.3175. Epub 2015 Jan 5.


To provide a more comprehensive understanding of the genes and evolutionary forces driving colorectal cancer (CRC) progression, we performed Sleeping Beauty (SB) transposon mutagenesis screens in mice carrying sensitizing mutations in genes that act at different stages of tumor progression. This approach allowed us to identify a set of genes that appear to be highly relevant for CRC and to provide a better understanding of the evolutionary forces and systems properties of CRC. We also identified six genes driving malignant tumor progression and a new human CRC tumor-suppressor gene, ZNF292, that might also function in other types of cancer. Our comprehensive CRC data set provides a resource with which to develop new therapies for treating CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenoma / genetics*
  • Adenoma / pathology
  • Animals
  • Biological Evolution
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cohort Studies
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • DNA Transposable Elements
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Genes, Tumor Suppressor
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mutagenesis, Insertional / methods*
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Sequence Analysis, DNA
  • Signal Transduction
  • Specific Pathogen-Free Organisms
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Xenograft Model Antitumor Assays


  • Carrier Proteins
  • DNA Transposable Elements
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • Transcription Factors
  • ZNF292 protein, human
  • Zfp292 protein, mouse