The Role of Developmental Genes in Chordoma

Chordoma is a rare tumor arising from notochordal remnants, and most often located at either end of the spinal axis. Recently gene expression analysis has revealed that brachyury, a tissue-specific transcription factor expressed in the nucleus of notochord cells, is highly expressed in chordoma, but was not found to be expressed in a wide variety of non-neoplastic tissues or 42 other types of neoplasms. Since brachyury is essential for notochord development and maintenance, we hypothesized that brachyury plays a pathogenic role in chordoma development and/or survival. To test this hypothesis, we propose to knock-down expression of brachyury in chordoma cells in vitro using RNAi techniques and assess the effect of reduced brachyury expression on cellular phenotype, including cellular proliferation, growth in soft agar, wound healing, and apoptosis. If our work further implicates brachyury in chordoma, future work would utilize that information to guide development of targeted therapeutics for chordoma.