Medulloblastoma: Role of OTX2 transcription factors

Abstract

Orthodenticle homeobox 2 (OTX2) is a -member of the highly conserved family of bicoid-like transcription factors that is responsible for the patterning of early brain development. It is primarily expressed in the rostral part of the embryo, corresponding to the presumptive fore- and mid-brain and disappears later in life. OTX2 is also a known oncogene for medulloblastoma, and aberrant over-expression has been correlated with poorer survival in medulloblastoma patients. Oncogenic OTX2 is implicated to function in the MYC pathway; however, the relationship of OTX2 to other common genomic pathways implicated in medulloblastoma, such as Notch and Epidermal Growth Factor Receptor, is unclear. Whether OTX2 is a member of one of these pathways or represents another interconnected pathway entirely remains to be elucidated. In OTX2-dependent medulloblastomas, such as the anaplastic histopathologic subtype, targeting OTX2 expression via siRNA or exogenously applied all-trans retinoic acid has shown promise in reducing cellular proliferation. Studies in tumors of common ontologic relationship further support the role of OTX2 as an oncogene in medulloblastoma and may serve as additional avenues to explore how OTX2 is overexpressed to support the growth and proliferation of OTX2-dependent medulloblastomas.