A Transposon-Based Genetic Screen in Mice Identifies Genes Altered in Colorectal Cancer

Starr, T. K., Allaei, R., Silverstein, K. A. T., Staggs, R. A., Sarver, A. L., Bergemann, T. L., Gupta, M., O'Sullivan, M. G., Matise, I., Dupuy, A. J., Collier, L. S., Powers, S., Oberg, A. L., Asmann, Y. W., Thibodeau, S. N., Tessarollo, L., Copeland, N. G., Jenkins, N. A., Cormier, R. T., Largaespada, D. A. (March 2009) A Transposon-Based Genetic Screen in Mice Identifies Genes Altered in Colorectal Cancer. Science, 323 (5922). pp. 1747-1750. ISSN 0036-8075

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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.

Item Type:	Paper
Uncontrolled Keywords:	TUMOR-SUPPRESSOR EXPRESSION CELLS METHYLATION INSTABILITY MUTAGENESIS EPITHELIUM MOUSE
Subjects:	bioinformatics diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics organism description > animal diseases & disorders > cancer > cancer types > colon cancer diseases & disorders > cancer > cancer types > colon cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function organism description > animal > mammal > rodent > mouse bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transposons diseases & disorders > cancer > cancer types
CSHL Authors:	Powers, Scott
Communities:	CSHL labs > Powers lab
Depositing User:	Matt Covey
Date:	27 March 2009
Date Deposited:	15 Feb 2013 20:34
Last Modified:	02 Oct 2019 19:45
PMCID:	PMC2743559
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/27473

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