A Transposon-Based Genetic Screen in Mice Identifies Genes Altered in Colorectal Cancer-Reference-Cited by-同舟云学术

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

Published:2009-03-27 Issue:5922 Volume:323 Page:1747-1750
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Starr Timothy K.¹²³⁴⁵,Allaei Raha¹²³⁴⁵,Silverstein Kevin A. T.¹²³⁴⁵,Staggs Rodney A.¹²³⁴⁵,Sarver Aaron L.¹²³⁴⁵,Bergemann Tracy L.¹²³⁴⁵,Gupta Mihir¹²³⁴⁵,O'Sullivan M. Gerard¹²³⁴⁵,Matise Ilze¹²³⁴⁵,Dupuy Adam J.¹²³⁴⁵,Collier Lara S.¹²³⁴⁵,Powers Scott¹²³⁴⁵,Oberg Ann L.¹²³⁴⁵,Asmann Yan W.¹²³⁴⁵,Thibodeau Stephen N.¹²³⁴⁵,Tessarollo Lino¹²³⁴⁵,Copeland Neal G.¹²³⁴⁵,Jenkins Nancy A.¹²³⁴⁵,Cormier Robert T.¹²³⁴⁵,Largaespada David A.¹²³⁴⁵

Affiliation:

1. Department of Genetics, Cell Biology and Development, Center for Genome Engineering, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.

2. Department of Biostatistics and Informatics, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.

3. Department of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA.

4. Department of Physical and Chemical Biology, Harvard College, Cambridge, MA 02138, USA.

5. College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108, USA.

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 .

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference27 articles.

1. The Genomic Landscapes of Human Breast and Colorectal Cancers

2. The onset and extent of genomic instability in sporadic colorectal tumor progression

3. Genome-wide expression patterns of invasion front, inner tumor mass and surrounding normal epithelium of colorectal tumors

4. H. Hayashiet al., Hum. Genet.120, 701 (2007).

5. Disruption of overlapping transcripts in the ROSA geo 26 gene trap strain leads to widespread expression of -galactosidase in mouse embryos and hematopoietic cells

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