Malignant peripheral nerve sheath tumor (MPNST) represents 5-10% of soft-tissue sarcomas, and can develop either sporadically, in patients with neurofibromatosis Type I (NF1), or in association with radiotherapy. Limited genetic information regarding their pathogenesis in humans has posed a challenge to developing authentic mouse models more reflective of the human disease. Recently, we discovered that these clinically distinct MPNST subtypes commonly share inactivating mutations in tumor suppressors NF1, CDKN2A, and PRC2 (Polycomb Repressive Complex 2). Using a combination of Cre-loxP-based genetically engineered mouse models (GEMMs) and stem/progenitor transplantation models, we show that inactivation of these tumor suppressors is sufficient to promote development of bona fide MPNSTs. We envision that further characterization of these models will provide a solid foundation for investigating MPNST biology and developing therapies in a genetically defined context more closely resembling the human disease.

This abstract is also being presented as Poster B18.

Citation Format: Amish J. Patel, Jessica J. Sher, Yu Chen, Ping Chi. Development and characterization of novel/genetically defined mouse models of malignant peripheral nerve sheath tumor for preclinical therapeutics testing [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr PR10.

©2018 American Association for Cancer Research.
2018
American Association for Cancer Research.