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A Transposon-Based Genetic Screen in Mice Identifies Genes Altered in Colorectal Cancer

  1. Author:
    Starr, T. K.
    Allaei, R.
    Silverstein, K.
    Staggs, R. A.
    Sarver, A. L.
    Bergemann, T. L.
    Gupta, M.
    O'Sullivan, M. G.
    Matise, I.
    Dupuy, A. J.
    Collier, L. S.
    Powers, S.
    Oberg, A. L.
    Asmann, Y. W.
    Thibodeau, S. N.
    Tessarollo, L.
    Copeland, T. D.

  2. Author Address

    Starr, Timothy K.; Allaei, Raha, Largaespada, David A.] Univ Minnesota, Dept Genet Cell Biol & Dev, Ctr Genome Engn, Masonic Canc Ctr, Minneapolis, MN 55455 USA. [Silverstein, Kevin A. T.; Staggs, Rodney A.; Sarver, Aaron L.] Univ Minnesota, Dept Biostat & Informat, Masonic Canc Ctr, Minneapolis, MN 55455 USA. [Bergemann, Tracy L.] Univ Minnesota, Sch Publ Hlth, Dept Biostat, Minneapolis, MN 55455 USA. [Gupta, Mihir] Harvard Univ, Dept Phys & Chem Biol, Cambridge, MA 02138 USA. [O'Sullivan, M. Gerard, Matise, Ilze] Univ Minnesota, Coll Vet Med, St Paul, MN 55108 USA. [Dupuy, Adam J.] Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. [Collier, Lara S.] Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA. [Powers, Scott] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Oberg, Ann L.; Asmann, Yan W.; Thibodeau, Stephen N.] Mayo Clin, Coll Med, Rochester, MN 55905 USA. [Tessarollo, Lino] NCI, Neural Dev Grp, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. [Copeland, Neal G.; Jenkins, Nancy A.] Inst Mol & Cell Biol, Singapore 138673, Singapore. [Cormier, Robert T.] Univ Minnesota, Sch Med, Duluth, MN 55812 USA.
    1. Year: 2009
  2. Journal: Science
    1. 323
    2. 5922
    3. Pages: 1747-1750
  4. Type of Article: Article
  1. Abstract:

    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.

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External Sources

  1. PMID: 19251594

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