OTX2 is critical for the maintenance and progression of Shh-independent medulloblastomas.

Journal Article (Journal Article)

OTX2 is a developmentally regulated transcription factor involved in early morphogenesis of the central nervous system. This gene is amplified and overexpressed in medulloblastoma cell lines, but the nature and extent of its genetic alterations in primary tumors have not been evaluated. Analysis of a large cohort of primary medulloblastomas revealed frequent focal copy number gain of a region minimally containing OTX2 as a single gene. OTX2 copy number gain was restricted to tumor subtypes that did not express a molecular signature of Wnt or Shh pathway activation. FISH analysis revealed copy number gain in a subset of cells within medulloblastoma samples, suggesting a late event in tumor progression. Gain of OTX2 copy number was associated with the presence of anaplastic histologic features and shorter survival in medulloblastoma patients. In support of a functional role, ectopic OTX2 expression enhanced proliferation and tumorigenicity of immortalized primary cells, whereas OTX2 knockdown in medulloblastoma cells prolonged the survival of animals bearing xenograft tumors. Mechanistic investigations revealed upregulation of MYC as a potential mechanism whereby OTX2 promotes tumor progression. Our findings define OTX2 as an important oncogenic driver in medulloblastoma.

Full Text

Duke Authors

Cited Authors

  • Adamson, DC; Shi, Q; Wortham, M; Northcott, PA; Di, C; Duncan, CG; Li, J; McLendon, RE; Bigner, DD; Taylor, MD; Yan, H

Published Date

  • January 1, 2010

Published In

Volume / Issue

  • 70 / 1

Start / End Page

  • 181 - 191

PubMed ID

  • 20028867

Pubmed Central ID

  • PMC2943736

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-09-2331


  • eng

Conference Location

  • United States