Keng, V. W., Villanueva, A., Chiang, D. Y., Dupuy, A. J., Ryan, B. J., Matise, I., Silverstein, K. A. T., 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., Largaespada, D. A. (March 2009) A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma. Nature Biotechnology, 27 (3). pp. 264-274. ISSN 1087-0156
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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR-RECEPTOR NF-KAPPA-B SLEEPING-BEAUTY IN-VITRO LIVER-CANCER EXPRESSION KINASE TUMOR ACTIVATION PATHWAY |
| Subjects: | bioinformatics diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics diseases & disorders > cancer > cancer types > liver cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transposons diseases & disorders > cancer > cancer types |
| CSHL Authors: | |
| Communities: | CSHL labs > Lowe lab CSHL labs > Powers lab |
| Depositing User: | Matt Covey |
| Date: | March 2009 |
| Date Deposited: | 21 Feb 2013 21:12 |
| Last Modified: | 21 Feb 2013 21:12 |
| PMCID: | PMC2712727 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/27348 |
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