@article{fb4c36d7fd87481494757dadb96e32ea,
title = "Impaired nonhomologous end-joining provokes soft tissue sarcomas harboring chromosomal translocations, amplifications, and deletions",
abstract = "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.",
author = "Sharpless, {Norman E.} and Ferguson, {David O.} and O'Hagan, {R{\'o}n{\'a}n C.} and Castrillon, {Diego H.} and Charles Lee and Farazi, {Paraskevi A.} and Scott Alson and James Fleming and Morton, {Cynthia C.} and Karen Frank and Lynda Chin and Alt, {Frederick W.} and DePinho, {Ronald A.}",
note = "Funding Information: The authors wish to thank A. Levine, M. Meyerson, J. You, A. Aguirre, and S. Chan for reagents, assistance and/or advice; members of the Dana-Farber Cancer Institute Belfer Cancer Genomics Center for assistance with array-CGH; and N. Bardeesy for critical reading of the manuscript. N.E.S. and F.A. are supported by the Howard Hughes Medical Institute. D.O.F. and D.H.C. are supported through National Institutes of Health K08 awards. R.A.D. is an American Cancer Society Professor. This work was supported by grants from the National Institutes of Health and the American Cancer Society.",
year = "2001",
doi = "10.1016/S1097-2765(01)00425-7",
language = "English (US)",
volume = "8",
pages = "1187--1196",
journal = "Molecular cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",
}