| First Author | Woo Y | Year | 2007 |
| Journal | Oncogene | Volume | 26 |
| Issue | 41 | Pages | 6010-20 |
| PubMed ID | 17384673 | Mgi Jnum | J:130286 |
| Mgi Id | MGI:3771435 | Doi | 10.1038/sj.onc.1210430 |
| Citation | Woo Y, et al. (2007) The nonhomologous end joining factor Artemis suppresses multi-tissue tumor formation and prevents loss of heterozygosity. Oncogene 26(41):6010-20 |
| abstractText | Nonhomologous end joining (NHEJ) is a critical DNA repair pathway, with proposed tumor suppression functions in many tissues. Mutations in the NHEJ factor ARTEMIS cause radiation-sensitive severe combined immunodeficiency in humans and may increase susceptibility to lymphoma in some settings. We now report that deficiency for Artemis (encoded by Dclre1c/Art in mouse) accelerates tumorigenesis in several tissues in a Trp53 heterozygous setting, revealing tumor suppression roles for NHEJ in lymphoid and non-lymphoid cells. We also show that B-lineage lymphomas in these mice undergo loss of Trp53 heterozygosity by allele replacement, but arise by mechanisms distinct from those in Art Trp53 double null mice. These findings demonstrate a general tumor suppression function for NHEJ, and reveal that interplay between NHEJ and Trp53 loss of heterozygosity influences the sequence of multi-hit oncogenesis. We present a model where p53 status at the time of tumor initiation is a key determinant of subsequent oncogenic mechanisms. Because Art deficient mice represent a model for radiation-sensitive severe combined immunodeficiency, our findings suggest that these patients may be at risk for both lymphoid and non-lymphoid cancers. |
