From Chordomas to Gliomas: Putting the Brakes on Brachyury

Abstract

Introduction: Chordomas are tumors that arise from the osseous spine and skull base and compromise 2%–4% of all bone cancers. The locally invasive nature of these cancers and the radio- and chemoresistance that they exhibit makes complete surgical resection and remission a major therapeutic challenge. Recent molecular interrogation of chordomas has revealed a critical gene duplication of the mesenchymal developmental transcription factor Brachyury (T gene) in all familial chordomas, suggesting a gain of function mutation. We hypothesize that the overexpression of Brachyury is a pivotal molecular event in the progression of chordomas and other notoriously aggressive malignancies of the neuroaxis, including gliomas and gliosarcomas.