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A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma

  1. Author:
    Keng, V. W.
    Villanueva, A.
    Chiang, D. Y.
    Dupuy, A. J.
    Ryan, B. J.
    Matise, I.
    Silverstein, K.
    Sarver, A.
    Starr, T. K.
    Akagi, K.
    Tessarollo, L.
    Collier, L. S.
    Powers, S.
    Lowe, S. W.
    Jenkins, N. A.
    Copeland, N. G.
    Llovet, J. M.

  2. Author Address

    Keng, Vincent W.; Ryan, Barbara J.; Matise, Ilze, Silverstein, Kevin A. T.; Sarver, Aaron, Starr, Timothy K.; Largaespada, David A.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55455 USA. [Keng, Vincent W.; Ryan, Barbara J.; Starr, Timothy K.; Largaespada, David A.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA. [Villanueva, Augusto, Llovet, Josep M.] Hosp Clin Barcelona, CIBERehd, IDIBAPS, HCC Translat Res Lab,BCLC Grp Liver Unit, E-08036 Barcelona, Spain. [Chiang, Derek Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chiang, Derek Y.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Chiang, Derek Y.] Broad Inst Harvard, Canc Program, Cambridge, MA 02142 USA. [Chiang, Derek Y.] MIT, Cambridge, MA 02142 USA. [Dupuy, Adam J.] Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. [Akagi, Keiko, Tessarollo, Lino] NCI, Frederick, MD 21702 USA. [Collier, Lara S.] Univ Wisconsin, Sch Pharm, Div Pharmaceut Sci, Madison, WI 53705 USA. [Powers, Scott, Lowe, Scott W.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Jenkins, Nancy A.; Copeland, Neal G.] Inst Mol & Cellular Biol, Singapore 138673, Singapore. [Llovet, Josep M.] Mt Sinai Sch Med, Mt Sinai Liver Canc Program, New York, NY 10029 USA. [Llovet, Josep M.] Inst Catalana Recerca & Estudis Avancats, Barcelona 08010, Spain.
    1. Year: 2009
  2. Journal: Nature Biotechnology
    1. 27
    2. 3
    3. Pages: 264-274
  4. Type of Article: Article
  1. Abstract:

    We describe a system that permits conditional mobilization of a Sleeping Beauty (SB) transposase allele by Cre recombinase to induce cancer specifically in a tissue of interest. To demonstrate its potential for developing tissue-specific models of cancer in mice, we limit SB transposition to the liver by placing Cre expression under the control of an albumin enhancer/promoter sequence and screen for hepatocellular carcinoma (HCC)-associated genes. From 8,060 nonredundant insertions cloned from 68 tumor nodules and comparative analysis with data from human HCC samples, we identify 19 loci strongly implicated in causing HCC. These encode genes, such as EGFR and MET, previously associated with HCC and others, such as UBE2H, that are potential new targets for treating this neoplasm. Our system, which could be modified to drive transposon-based insertional mutagenesis wherever tissue-specific Cre expression is possible, promises to enhance understanding of cancer genomes and identify new targets for therapeutic development.

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External Sources

  1. PMID: 19234449

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