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Publication : Therapy-induced malignant neoplasms in Nf1 mutant mice.

First Author  Chao RC Year  2005
Journal  Cancer Cell Volume  8
Issue  4 Pages  337-48
PubMed ID  16226708 Mgi Jnum  J:103509
Mgi Id  MGI:3610243 Doi  10.1016/j.ccr.2005.08.011
Citation  Chao RC, et al. (2005) Therapy-induced malignant neoplasms in Nf1 mutant mice. Cancer Cell 8(4):337-48
abstractText  Therapy-induced cancers are a severe complication of genotoxic therapies. We used heterozygous Nf1 mutant mice as a sensitized genetic background to investigate tumor induction by radiation (RAD) and cyclophosphamide (CY). Mutagen-exposed Nf1(+/-) mice developed secondary cancers that are common in humans, including myeloid malignancies, sarcomas, and breast cancers. RAD cooperated strongly with heterozygous Nf1 inactivation in tumorigenesis. Most of the solid tumors showed loss of the wild-type Nf1 allele but retained two Trp53 alleles. Comparative genomic hybridization demonstrated distinct patterns of copy number aberrations in sarcomas and breast cancers from Nf1 mutant mice, and tumor cell lines showed deregulated Ras signaling. Nf1(+/-) mice provide a tractable model for investigating the pathogenesis of common mutagen-induced cancers and for testing preventive strategies.
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