Sarcoma represents a class of tumors arising from mesenchymal tissue. New approaches that target sarcoma-specific molecular alterations hold a promise of more effective therapies. Currently available sarcoma models do not accurately resemble relevant properties of the human disease and very often are inadequate for predicting the efficacy of investigational drugs in preclinical settings. Thus, in order to test novel targeted therapies, it is essential to develop in vivo models of sarcomas.

To this end, we have created a panel of well-characterized xenografts of primary human sarcomas that represent a spectrum of histotypes. Specifically, we transplanted intact human sarcomas under the skin of immunodeficient mice. We then compared the morphologic, phenotypic, and genetic characteristics of the tumor tissues before and after implantation in recipient mice.

To date, we have implanted into Nu/Nu recipients tumor tissue fragments from 32 gastrointestinal stromal tumors (GIST) 10 dedifferentiated liposarcomas and 6 leiomyosarcomas. Successful tumor growth was detected in 86% cases of GIST, 44% of liposarcomas and 33% of leiomyosarcomas. Upon serial transplantation, 35% of GISTs, 44% of liposarcomas and 33% of leiomyosarcomas have grown beyond passage F3. Histological analysis of the primary tumors and corresponding xenografts revealed that morphology and immunophenotype (c-Kit status for GISTs, MDM2 for liposarcomas, Smooth Muscle Actin for leiomyosarcomas) was retained throughout all passages. Moreover, all major genetic abnormalities present in the primary tumors were retained in the xenografts, as revealed by genome-wide Single Nucleotide Polymorphism (SNP) array analyses.

Our results show that this approach can be used to generate animal models that faithfully reproduce characteristics of human intact tumors. These models can be used for in vivo preclinical drug testing, diagnostic and prognostic molecular markers discovery, and for identification of molecular mechanisms of drug resistance.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4197.