Medulloblastoma is one of the most prevalent pediatric brain malignancies, accounting for approximately 20% of all primary CNS tumors in children under the age of 19. OTX2 is the member of a highly conserved family of bicoid-like homeodomain transcription factors responsible for the regulation of cerebellar development and of current investigational interest in the tumorigenesis of medulloblastoma. Recent studies have revealed that Group 3 and Group 4 medulloblastomas show marked overexpression of OTX2 with a concurrent amplification of the MYC and MYCN oncogenes, respectively, correlating with anaplasticity and unfavorable patient outcomes. More recent attempts at elucidating the mechanism of OTX2-driven oncogenesis at the cellular level has also revealed that OTX2 may confer stem-cell like properties to tumor cells via epigenetic regulation. The review seeks to define the interaction pathways and binding partners involved in OTX2 function, its usefulness as a molecular marker for risk stratification and prognosis, and the mechanism by which it drives tumor maintenance. Additionally, it will preview unpublished data by our group highlighting the unanticipated involvement of OTX2 in the control of cellular metabolism.
Keywords: MYC; OTX2; cancer metabolism; histone modification; medulloblastoma.