Journal article
A Transposon-Based Genetic Screen in Mice Identifies Genes Altered in Colorectal Cancer
Science (American Association for the Advancement of Science), Vol.323(5922), pp.1747-1750
03/27/2009
DOI: 10.1126/science.1163040
PMCID: PMC2743559
PMID: 19251594
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 to 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 new candidate genes that had not previously been implicated in CRC, including
POLI, PTPRK
, and
RSPO2
.
Details
- Title: Subtitle
- A Transposon-Based Genetic Screen in Mice Identifies Genes Altered in Colorectal Cancer
- Creators
- Timothy K Starr - Department of Genetics, Cell Biology and Development, Arnold & Mabel Beckman Center for Transposon Research, the Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USARaha Allaei - Department of Genetics, Cell Biology and Development, Arnold & Mabel Beckman Center for Transposon Research, the Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USAKevin A. T Silverstein - Biostatistics and Informatics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USARodney A Staggs - Biostatistics and Informatics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USAAaron L Sarver - Biostatistics and Informatics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USATracy L Bergemann - Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USAMihir Gupta - Harvard University, Cambridge, MAM. Gerard O’Sullivan - College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108Ilze Matise - College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108Adam J Dupuy - Anatomy and Cell Biology, University of Iowa, Iowa City, IA, 52242, USALara S Collier - School of Pharmacy, University of Wisconsin, Madison, WI 53705, USAScott Powers - Cold Spring Harbors Laboratory, Cold Spring Harbor, NY 11724, USAAnn L Oberg - Mayo Clinic College of Medicine, Rochester, MN 55905, USAYan W Asmann - Mayo Clinic College of Medicine, Rochester, MN 55905, USAStephen N Thibodeau - Mayo Clinic College of Medicine, Rochester, MN 55905, USALino Tessarollo - Neural Development Group, Mouse Cancer Genetics program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702Neal G Copeland - Institute of Molecular and Cell Biology, Singapore, 138673Nancy A Jenkins - Institute of Molecular and Cell Biology, Singapore, 138673Robert T Cormier - University of Minnesota Medical School, Duluth, MN 55812, USADavid A Largaespada - Department of Genetics, Cell Biology and Development, Arnold & Mabel Beckman Center for Transposon Research, the Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.323(5922), pp.1747-1750
- DOI
- 10.1126/science.1163040
- PMID
- 19251594
- PMCID
- PMC2743559
- NLM abbreviation
- Science
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Language
- English
- Date published
- 03/27/2009
- Academic Unit
- Anatomy and Cell Biology; Pathology
- Record Identifier
- 9984025375702771
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