Large-scale mutagenesis in p19(ARF)- and p53-deficient mice identifies cancer genes and their collaborative networks

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2008
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Uren, Anthony G.
Kool, Jaap
Ridder, Jeroen de
Mattison, Jenny
Uitert, Miranda van
Lagcher, Wendy
Sie, Daoud
Tanger, Ellen
Cox, Tony
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p53 and p19(ARF) are tumor suppressors frequently mutated in human tumors. In a high-throughput screen in mice for mutations collaborating with either p53 or p19(ARF) deficiency, we identified 10,806 retroviral insertion sites, implicating over 300 loci in tumorigenesis. This dataset reveals 20 genes that are specifically mutated in either p19(ARF)-deficient, p53-deficient or wild-type mice (including Flt3, mmu-mir-106a-363, Smg6, and Ccnd3), as well as networks of significant collaborative and mutually exclusive interactions between cancer genes. Furthermore, we found candidate tumor suppressor genes, as well as distinct clusters of insertions within genes like Flt3 and Notch1 that induce mutants with different spectra of genetic interactions. Cross species comparative analysis with aCGH data of human cancer cell lines revealed known and candidate oncogenes (Mmp13, Slamf6, and Rreb1) and tumor suppressors (Wwox and Arfrp2). This dataset should prove to be a rich resource for the study of genetic interactions that underlie tumorigenesis.

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ISO 690UREN, Anthony G., Jaap KOOL, Konstantin MATENTZOGLU, Jeroen de RIDDER, Jenny MATTISON, Miranda van UITERT, Wendy LAGCHER, Daoud SIE, Ellen TANGER, Tony COX, Marcel REINDERS, Tim J. HUBBARD, Jane ROGERS, Jos JONKERS, Lodewyk WESSELS, David J. ADAMS, Maarten van LOHUIZEN, Anton BERNS, 2008. Large-scale mutagenesis in p19(ARF)- and p53-deficient mice identifies cancer genes and their collaborative networks. In: Cell. 2008, 133(4), pp. 727-741. ISSN 0092-8674. eISSN 1097-4172. Available under: doi: 10.1016/j.cell.2008.03.021
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@article{Uren2008Large-1190,
  year={2008},
  doi={10.1016/j.cell.2008.03.021},
  title={Large-scale mutagenesis in p19(ARF)- and p53-deficient mice identifies cancer genes and their collaborative networks},
  number={4},
  volume={133},
  issn={0092-8674},
  journal={Cell},
  pages={727--741},
  author={Uren, Anthony G. and Kool, Jaap and Matentzoglu, Konstantin and Ridder, Jeroen de and Mattison, Jenny and Uitert, Miranda van and Lagcher, Wendy and Sie, Daoud and Tanger, Ellen and Cox, Tony and Reinders, Marcel and Hubbard, Tim J. and Rogers, Jane and Jonkers, Jos and Wessels, Lodewyk and Adams, David J. and Lohuizen, Maarten van and Berns, Anton}
}
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