A transposon-based genetic screen in mice identifies genes altered in colorectal cancer by Starr Timothy K, Allaei Raha, Silverstein Kevin A T, Staggs Rodney A, Sarver Aaron L, Bergemann Tracy L, Gupta Mihir, O'Sullivan M Gerard, Matise Ilze, Dupuy Adam J, Collier Lara S, Powers Scott, Oberg Ann L, Asmann Yan W, Thibodeau Stephen N, Tessarollo Lino, Copeland Neal G, Jenkins Nancy A, Cormier Robert T, Largaespada David A in Science (New York, N.Y.) (2009). PubMed

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 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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