title: Establishment and characterization of a primary human chordoma xenograft model.
abstract: OBJECTIVE
  Chordomas are rare tumors arising from remnants of the notochord. Because of the challenges in achieving a complete 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, the authors aimed to develop a primary chordoma xenograft model.
  
  
  METHODS
  The authors implanted independent tumor samples from 2 patients into athymic nude mice. The resulting xenograft line was characterized by histopathological analysis and immunohistochemical staining. The patient's tumor and serial passages of the xenograft were genomically analyzed using a 660,000 single-nucleotide polymorphism array.
  
  
  RESULTS
  A serially transplantable xenograft was established from one of the 2 patient samples. Histopathological analysis and immunohistochemical staining for S100 protein, epithelial membrane antigen, and cytokeratin AE1/AE3 of the primary patient sample and the xenografts confirmed that the xenografts were identical to the original chordoma obtained from the patient. Immunohistochemical staining and western blot analysis confirmed the presence of brachyury, a recently described marker of chordomas, in the tumor from the patient and each of the xenografts. Genome-wide variation was assessed between the patient's tumor and the xenografts and was found to be more than 99.9% concordant.
  
  
  CONCLUSIONS
  To the best of their knowledge, the authors have established the first primary chordoma xenograft that will provide a useful preclinical model for this disease and a platform for therapeutic development.
authors.affiliation: Department of Neurosurgery, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: I-Mei
authors.initials: IM
authors.lastname: Siu
authors.forename: Vafi
authors.initials: V
authors.lastname: Salmasi
authors.forename: Brent A
authors.initials: BA
authors.lastname: Orr
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Zev A
authors.initials: ZA
authors.lastname: Binder
authors.forename: Christine
authors.initials: C
authors.lastname: Tran
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishii
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riggins
authors.forename: Christine L
authors.initials: CL
authors.lastname: Hann
authors.forename: Gary L
authors.initials: GL
authors.lastname: Gallia
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002817:Chordoma / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013120:Spinal Cord Neoplasms / Q000473:pathology*; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor