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Publication : A transposon-based genetic screen in mice identifies genes altered in colorectal cancer.

First Author  Starr TK Year  2009
Journal  Science Volume  323
Issue  5922 Pages  1747-50
PubMed ID  19251594 Mgi Jnum  J:146887
Mgi Id  MGI:3838886 Doi  10.1126/science.1163040
Citation  Starr TK, et al. (2009) A transposon-based genetic screen in mice identifies genes altered in colorectal cancer. Science 323(5922):1747-50
abstractText  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 with 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 candidate genes that had not previously been implicated in CRC, including POLI, PTPRK, and RSPO2.
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