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A transposon-based genetic screen in mice identifies genes altered in colorectal cancer.

Human colorectal cancers (CRCs) display a large number of genetic and epigenetic alterations, some of which are causally involved in tumorigenesis (drivers) and others that have little functional impact (passengers). To help distinguish between these two classes of alterations, we used a transposon-based genetic screen in mice to identify candidate genes for CRC. Mice harboring mutagenic Sleeping Beauty (SB) transposons were crossed with mice expressing SB transposase in gastrointestinal tract epithelium. Most of the offspring developed intestinal lesions, including intraepithelial neoplasia, adenomas, and adenocarcinomas. Analysis of over 16,000 transposon insertions identified 77 candidate CRC genes, 60 of which are mutated and/or dysregulated in human CRC and thus are most likely to drive tumorigenesis. These genes include APC, PTEN, and SMAD4. The screen also identified 17 candidate genes that had not previously been implicated in CRC, including POLI, PTPRK, and RSPO2.

Pubmed ID: 19251594


  • Starr TK
  • Allaei R
  • Silverstein KA
  • Staggs RA
  • Sarver AL
  • Bergemann TL
  • Gupta M
  • O'Sullivan MG
  • Matise I
  • Dupuy AJ
  • Collier LS
  • Powers S
  • Oberg AL
  • Asmann YW
  • Thibodeau SN
  • Tessarollo L
  • Copeland NG
  • Jenkins NA
  • Cormier RT
  • Largaespada DA


Science (New York, N.Y.)

Publication Data

March 27, 2009

Associated Grants

  • Agency: NCI NIH HHS, Id: R01 CA113636
  • Agency: NCI NIH HHS, Id: R01 CA113636-01A1

Mesh Terms

  • Adenocarcinoma
  • Adenoma
  • Animals
  • Carcinoma in Situ
  • Colorectal Neoplasms
  • Crosses, Genetic
  • DNA Transposable Elements
  • Gene Amplification
  • Gene Deletion
  • Gene Expression Regulation, Neoplastic
  • Genes, APC
  • Genes, Neoplasm
  • Genetic Testing
  • Humans
  • Mice
  • Mice, Transgenic
  • Monte Carlo Method
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • PTEN Phosphohydrolase
  • Smad4 Protein