| First Author | Sharpless NE | Year | 2001 |
| Journal | Mol Cell | Volume | 8 |
| Issue | 6 | Pages | 1187-96 |
| PubMed ID | 11779495 | Mgi Jnum | J:88792 |
| Mgi Id | MGI:3037169 | Doi | 10.1016/s1097-2765(01)00425-7 |
| Citation | Sharpless NE, et al. (2001) Impaired nonhomologous end-joining provokes soft tissue sarcomas harboring chromosomal translocations, amplifications, and deletions. Mol Cell 8(6):1187-96 |
| abstractText | Although nonhomologous end-joining (NHEJ) deficiency has been shown to accelerate lymphoma formation in mice, its role in suppressing tumors in cells that do not undergo V(D)J recombination is unclear. Utilizing a tumor-prone mouse strain (ink4a/arf(-/-)), we examined the impact of haploinsufficiency of a NHEJ component, DNA ligase IV (Lig4), on murine tumorigenesis. We demonstrate that lig4 heterozygosity promotes the development of soft-tissue sarcomas that possess clonal amplifications, deletions, and translocations. That these genomic alterations are relevant in tumorigenesis is supported by the finding of frequent mdm2 amplification, a known oncogene in human sarcoma. Together, these findings support the view that loss of a single lig4 allele results in NHEJ activity being sufficiently reduced to engender chromosomal aberrations that drive non-lymphoid tumorigenesis. |
