TY - JOUR
T1 - A transposon-based genetic screen in mice identifies genes altered in colorectal cancer
AU - Starr, Timothy K.
AU - Allaei, Raha
AU - Silverstein, Kevin A.T.
AU - Staggs, Rodney A.
AU - Sarver, Aaron L.
AU - Bergemann, Tracy L.
AU - Gupta, Mihir
AU - Gerard O'Sullivan, M.
AU - Matise, Ilze
AU - Dupuy, Adam J.
AU - Collier, Lara S.
AU - Powers, Scott
AU - Oberg, Ann L.
AU - Asmann, Yan W.
AU - Thibodeau, Stephen N.
AU - Tessarollo, Lino
AU - Copeland, Neal G.
AU - Jenkins, Nancy A.
AU - Cormier, Robert T.
AU - Largaespada, David A.
PY - 2009/3/27
Y1 - 2009/3/27
N2 - 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.
AB - 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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U2 - 10.1126/science.1163040
DO - 10.1126/science.1163040
M3 - Article
C2 - 19251594
AN - SCOPUS:63049105067
SN - 0036-8075
VL - 323
SP - 1747
EP - 1750
JO - Science
JF - Science
IS - 5922
ER -