Large-scale mutagenesis in p19(ARF)- and p53-deficient mice identifies cancer genes and their collaborative networks
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 gene...
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| Veröffentlicht in: | Cell 2008-05, Vol.133 (4), p.727 |
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| creator | Uren, Anthony G Kool, Jaap Matentzoglu, Konstantin de Ridder, Jeroen Mattison, Jenny van Uitert, Miranda Lagcher, Wendy Sie, Daoud Tanger, Ellen Cox, Tony Reinders, Marcel Hubbard, Tim J Rogers, Jane Jonkers, Jos Wessels, Lodewyk Adams, David J van Lohuizen, Maarten Berns, Anton |
| description | 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. |
| doi_str_mv | 10.1016/j.cell.2008.03.021 |
| format | Article |
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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). 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This dataset should prove to be a rich resource for the study of genetic interactions that underlie tumorigenesis.</description><subject>Animals</subject><subject>Cell Line, Tumor</subject><subject>Cloning, Molecular</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</subject><subject>Gene Regulatory Networks</subject><subject>Genes, p53</subject><subject>Genes, Tumor Suppressor</subject><subject>Genomics - methods</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mutagenesis, Insertional</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - metabolism</subject><subject>Sequence Analysis, DNA</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1j0FLAzEUhIMgtlb_gAfJUQ-75mWbTXIsxapQEETPJXl5ram722WTKv57S9XTDMw3A8PYFYgSBNR32xKpaUophClFVQoJJ2wMwupiClqO2HlKW3EIlVJnbARmapTRdszy0g0bKhK6hni7z25DHaWYeOx4D_Zm9rK4LbjrAu9VVQRaR4zUZd5GJB7DwcZ1pMTRdUgDP7aPeH6nOHDcNY3zu8Hl-Em8o_y1Gz7SBTtduybR5Z9O2Nvi_nX-WCyfH57ms2XRS2FzUaHz6NEBGfRgvVY1SRGMJGUoeC39VIEGRCRdgQoWawEeDkjw0pq6mrDr391-71sKq36IrRu-V__3qx9R5l0O</recordid><startdate>20080516</startdate><enddate>20080516</enddate><creator>Uren, Anthony G</creator><creator>Kool, Jaap</creator><creator>Matentzoglu, Konstantin</creator><creator>de Ridder, Jeroen</creator><creator>Mattison, Jenny</creator><creator>van Uitert, Miranda</creator><creator>Lagcher, Wendy</creator><creator>Sie, Daoud</creator><creator>Tanger, Ellen</creator><creator>Cox, Tony</creator><creator>Reinders, Marcel</creator><creator>Hubbard, Tim J</creator><creator>Rogers, Jane</creator><creator>Jonkers, Jos</creator><creator>Wessels, Lodewyk</creator><creator>Adams, David J</creator><creator>van Lohuizen, Maarten</creator><creator>Berns, Anton</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20080516</creationdate><title>Large-scale mutagenesis in p19(ARF)- and p53-deficient mice identifies cancer genes and their collaborative networks</title><author>Uren, Anthony G ; 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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). 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| ispartof | Cell, 2008-05, Vol.133 (4), p.727 |
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| source | MEDLINE; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Cell Line, Tumor Cloning, Molecular Cyclin-Dependent Kinase Inhibitor p16 - genetics Cyclin-Dependent Kinase Inhibitor p16 - metabolism Gene Regulatory Networks Genes, p53 Genes, Tumor Suppressor Genomics - methods Humans Mice Mice, Knockout Mutagenesis, Insertional Neoplasms - genetics Neoplasms - metabolism Sequence Analysis, DNA Tumor Suppressor Protein p53 - metabolism |
| title | Large-scale mutagenesis in p19(ARF)- and p53-deficient mice identifies cancer genes and their collaborative networks |
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