References
Query Results -- Details
MGI Accession ID: MGI:3839818
J Number: J:147264
Other Accession IDs:
Title: A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma.
Authors: Keng VW; Villanueva A; Chiang DY; Dupuy AJ; Ryan BJ; Matise I; Silverstein KA; Sarver A; Starr TK; Akagi K; Tessarollo L; Collier LS; Powers S; Lowe SW; Jenkins NA; Copeland NG; Llovet JM; Largaespada DA
Journal: Nat Biotechnol
Volume: 27
Issue: 3
Date: 2009 Mar
Year: 2009
Pages: 264-74
Review Status: Peer Reviewed
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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