Therapy-induced malignant neoplasms in Nf1 mutant mice

Richard C. Chao, Urszula Pyzel, Jane Fridlyand, Yien Ming Kuo, Lewis Teel, Jennifer Haaga, Alexander Borowsky, Andrew Horvai, Scott C. Kogan, Jeannette Bonifas, Bing Huey, Tyler E. Jacks, Donna G. Albertson, Kevin M. Shannon

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)337-348
Number of pages12
JournalCancer Cell
Issue number4
StatePublished - Oct 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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