Abstract 5197: Patient-derived xenograft (PDX) models of soft tissue sarcoma (STS): a preclinical platform for early drug testing
Authors: Wozniak Agnieszka , Cornillie Jasmien , Gebreyohannes Yemarshet K. , Boeckx Bram , Li Haifu , Van Looy Thomas , Floris Giuseppe , Wellens Jasmien , Vreys Lise , Hompes Daphne , Stas Marguerite , Sinnaeve Friedl , Lambrechts Diether , Debiec-Rychter Maria , Sciot Raf , Schoffski Patrick 
Published: July 2016

Abstract
Background: STS constitutes a rare and very heterogeneous family of mesenchymal tumors. The limited treatment options available for advanced STS underline the need for reliable preclinical models to test novel therapeutic strategies.
Methods: A panel of patient-derived xenografts (PDX) was established by subcutaneous implantation of fresh, surgically resected tumor specimens in immunodeficient athymic nude NMRI mice. Once tumor growth was observed, pieces of tumor were re-transplanted to next generations of mice. At each passage tumor fragments were collected for histolopathological and molecular characterization. A model was considered established after observing stable histological and molecular features for at least two passages. To evaluate the stability of the genomic profile we performed low-coverage whole-genome sequencing on DNA isolated from tumors obtained from at least two passages. In addition RNA-seq was used to better characterize the mutational profile of the ex-mouse tumors.
Results: Until now 139 STS samples from consenting patients treated at the University Hospitals, Leuven, Belgium, have been transplanted. Twenty six well-characterized, stable STS PDX models have been established, maintaining the histopathological and molecular features of the original tumor. Seventeen models, analyzed with low-coverage DNA sequencing, showed a stable genomic profile in at least two different tumor passages. At this point the panel includes models of gastrointestinal stromal tumor (6 models), myxofibrosarcoma (5), dedifferentiated liposarcoma (3), malignant peripheral nerve sheath tumor (3), synovial sarcoma (2), leiomyosarcoma (3) epithelioid haemangioendothelioma (1), mesenchymal chondrosarcoma (1) and undifferentiated high grade sarcoma (2). Some of these models have already been successfully used for in vivo testing of novel agents, including both targeted and cytotoxic (pro-)drugs, and results served as a rationale for at least four prospective clinical trials. In addition 22 other xenografts are still in early stages of engraftment, not yet fulfilling our criteria of an “established model”.
Conclusion: Our panel of mesenchymal PDX models is characterized by stable histological and molecular features. These clinically well-annotated models can contribute to reliable preclinical studies for new anticancer treatments for STS. The availability of unique, rare STS xenografts also allows to study the biology of these diseases. The platform is made available to collaborators from academia and industry.
Citation Format: Agnieszka Wozniak, Jasmien Cornillie, Yemarshet K. Gebreyohannes, Bram Boeckx, Haifu Li, Thomas Van Looy, Giuseppe Floris, Jasmien Wellens, Lise Vreys, Daphne Hompes, Marguerite Stas, Friedl Sinnaeve, Diether Lambrechts, Maria Debiec-Rychter, Raf Sciot, Patrick Schoffski. Patient-derived xenograft (PDX) models of soft tissue sarcoma (STS): a preclinical platform for early drug testing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5197.