Successful generation of patient-derived xenografts and cell lines as preclinical models for sarcomas.

Abstract

e22549 Background: The establishment of patient-derived preclinical models has been a challenge issue in sarcomas, because of the rarity of diseases. We report our successful experience in establishing patient-derived sarcoma xenografts and cell lines. Methods: Tumor tissue samples from sarcoma patients undergoing surgery were collected by a team of orthopedicians and pathologists. Small tumor fragments were subcutaneously transplanted to immunodeficient NOG mice. The other part was used to establish a cell line using serum-containing media. The omics profiling was performed to examine the preservation of molecular backgrounds during the model establishment. Effects of FDA-approved drugs were examined in the established models. Results: Since April 2014, tumor samples from 246 sarcoma cases have been processed. The sample characteristics are summarized in the table. Currently we have established PDXs and cell lines from 39 and 27 cases, respectively. Xenografts and cell lines were established from unique sarcomas such as CIC-DUX4 fusion positive sarcoma, extraskeletal osteosarcoma, primary leiomyosarcoma of bone, and alveolar soft part sarcoma. A take rate of xenografts and cell lines varied among the sarcoma types. Omics profiles considerably changed during the process of model establishment. Anti-cancer drugs with significant tumor suppressive effects were detected. Conclusions: Our patient-derived cancer models will facilitate translational sarcoma research. The original biological features preserved in the xenografts and cell lines should be clarified to optimize the utility of sarcoma models. Currently, our cell lines are available for the academic researchers upon a request.