Establishment and Initial Characterization of a Primary Human Chordoma Xenograft Model

Chordomas are rare tumors arising from remnants of the notochord. Because of the challenges in achieving a complete surgical resection, the radioresistant nature of these tumors, and the lack of effective chemotherapeutics, the median survival for patients with chordomas is approximately 6 years. Reproducible preclinical model systems that closely mimic the original patient's tumor are essential for the development and evaluation of effective therapeutics. Currently, there are only a few established chordoma cell lines and no primary xenograft model. In this study, we aimed to develop a primary chordoma xenograft model and implanted four independent patient tumor samples into athymic nude mice. A serially transplantable xenograft was established from one of these patient samples. Histopathological analysis and immunohistochemical staining for S-100, EMA, and cytokeratin AE1/AE3 of the primary patient sample and the xenografts confirmed the xenografts were identical to the original patient chordoma. Immunohistochemical staining and western analysis confirmed the presence of Brachyury, a marker of chordomas, in the patient tumor and each of the xenografts. Genome-wide variation was assessed between the patient's tumor and the xenografts and found to be > 99.9% concordant. We have established, to the best of our knowledge, the first primary chordoma xenograft that will provide a useful preclinical model for this disease and a platform for therapeutic development.