Journal article
A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma
Nature biotechnology, Vol.27(3), pp.264-274
2009
DOI: 10.1038/nbt.1526
PMCID: PMC2712727
PMID: 19234449
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.
Details
- Title: Subtitle
- A conditional transposon-based insertional mutagenesis screen for genes associated with mouse hepatocellular carcinoma
- Creators
- Vincent W KENG - Masonic Cancer CenterAugusto VILLANUEVA - BCLC Group-Liver Unit, HCC Translational Research Laboratory, IDIBAPS, CIBERehd, Hospital Clinic, Barcelona 08036, SpainLino TESSAROLLO - National Cancer Institute, Frederick, Maryland 21702, United StatesLara S COLLIER - Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53705, United StatesScott POWERS - Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, United StatesScott W LOWE - Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, United StatesNancy A JENKINS - Institute of Molecular and Cellular Biology, Singapore 138673, SingaporeNeal G COPELAND - Institute of Molecular and Cellular Biology, Singapore 138673, SingaporeJosep M LLOVET - Mount Sinai Liver Cancer Program, Mount Sinai School of Medicine, New York, New York 10029, United StatesDavid A LARGAESPADA - Masonic Cancer CenterDerek Y CHIANG - Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United StatesAdam J DUPUY - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52242, United StatesBarbara J RYAN - Masonic Cancer CenterIlze MATISE - Masonic Cancer CenterKevin A. T SILVERSTEIN - Masonic Cancer CenterAaron SARVER - Masonic Cancer CenterTimothy K STARR - Masonic Cancer CenterKeiko AKAGI - National Cancer Institute, Frederick, Maryland 21702, United States
- Resource Type
- Journal article
- Publication Details
- Nature biotechnology, Vol.27(3), pp.264-274
- DOI
- 10.1038/nbt.1526
- PMID
- 19234449
- PMCID
- PMC2712727
- NLM abbreviation
- Nat Biotechnol
- ISSN
- 1087-0156
- eISSN
- 1546-1696
- Publisher
- Nature Publishing Group; New York, NY
- Language
- English
- Date published
- 2009
- Academic Unit
- Anatomy and Cell Biology; Pathology
- Record Identifier
- 9984025375502771
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