Author/Authors :
Anthony G. Uren، نويسنده , , Jaap Kool، نويسنده , , Konstantin Matentzoglu، نويسنده , , Jeroen de Ridder، نويسنده , , Jenny Mattison، نويسنده , , Miranda van Uitert، نويسنده , , Wendy Lagcher، نويسنده , , Daoud Sie، نويسنده , , Ellen Tanger، نويسنده , , Tony Cox، نويسنده , , Marcel Reinders، نويسنده , , Tim J. Hubbard، نويسنده , , Jane Rogers، نويسنده , , Jos Jonkers، نويسنده , , Lodewyk Wessels، نويسنده , , David J. Adams and ...[et al.]، نويسنده , , Maarten van Lohuizen، نويسنده , , Anton Berns، نويسنده ,
Abstract :
p53 and p19ARF are tumor suppressors frequently mutated in human tumors. In a high-throughput screen in mice for mutations collaborating with either p53 or p19ARF 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 p19ARF-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.
