Introduction: Subtle genetic differences between clival chordomas and sacral chordomas have been described by our group. However, the only patient-derived tumor xenograft models for chordoma currently available have been established from sacral or extra-axial chordoma. Patient-derived xenografts retain the genetic features of the parent tumors more readily than cell line in culture. In order to further study the biology and genetics of clival chordoma we sought to establish a clival chordoma patient-derived xenograft tumor line.

Methods: A recurrent clival chordoma specimen was obtained through a transphenoidal endoscopic approach. The specimen was immediately placed in saline and cooled in an ice bath. Under sterile conditions, the tumor was morcelized and mixed into a Matrigel slurry. Subcutaneous implantation of the solidifying matrix-tissue slurry was performed in a pocket directly above the subocciptal musculature and occipital skull in NOD/SCID mice.

Results: Tumors developed in 2 of 2 implanted mice after 5 months. The tumors have been passaged serially and are now in the 4th generation of mice. Brachyury staining and physaliferous cell architecture was demonstrated in the first generation of tumors. Genomic and proteomic profiling of this tumor xenograft line is in progress.

Conclusions: We have established a patient-derived clival chordoma xenograft tumor line that can be used in the future to study the biology, genetics, and novel treatment approaches in these aggressive tumors for which there are currently few good therapeutic options.

Patient Care: We hope to use patient-derived xenograft tumor line to investigate the growth characteristics, genetics, and biology of clival chordomas as well as for testing of novel therapies.

Learning Objectives: Understand the genomic differences between clival and sacral chordomas Understand how a patient-derived xenograft model can be used to advance chordoma research

References: 1. Diaz RJ, Guduk M, Romagnuolo R, Smith CA, Northcott P, Shih D, Berisha F, Flanagan A, Munoz DG, Cusimano MD, Pamir MN, Rutka JT (2012). High-resolution whole-genome analysis of skull base chordomas implicates FHIT loss in chordoma pathogenesis. Neoplasia. Sep;14(9):788-98. 2.Diaz RJ, Cusimano M (2011) The biological basis for modern treatment of chordoma. J Neurooncol. Sep;104(2):411-22.