Abstract 3427A: Focal fractionated irradiation induces specific malignancies in a dose-dependent manner in Nf1 mutant mice

• Published in: Cancer research (Chicago, Ill.) Ill.), 2010-04, Vol.70 (8_Supplement), p.3427-3427A
• Main Authors: Nakamura, Jean L., Phong, Connie, Pinarbasi, Emile, Kogan, Scott C., Vandenberg, Scott, Horvai, Andrew E., Faddegon, Bruce A., Houseman, Benjamin T., Pieper, Russell O., Shannon, Kevin
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM10-3427A

Purpose: Secondary malignant neoplasms (SMNs) are a severe late complication of radiotherapy (RT). However little is known regarding the influence of radiation dose or genetic factors on this risk. Mutations in the NF1 tumor suppressor gene cause neurofibromatosis type I (NF1), and clinical observations suggest that affected persons are at increased risk of developing radiation-induced SMNs. NF1 encodes a GTPase activating protein that negatively regulates Ras signaling networks. We administered fractionated cranial irradiation (CI) to heterozygous Nf1 mutant (Nf1+/−) mice in an effort to accurately model common human SMNs. Materials and Methods: 121 C57BL6-Sv129 Nf1+/− and control wild-type (WT) mice were assigned to one of three CI treatment regimens: 0 Gy, 15 Gy (5 daily doses of 3 Gy), or 30 Gy (10 daily doses of 3 Gy). Results: Mice were observed for 18 months after CI or until they developed signs of disease requiring euthanasia. Kaplan-Meier analyses and log-rank tests demonstrate that Nf1 heterozygosity and radiotherapy are independently associated with significantly greater risks of death after CI (p