Identification of tumor precursor cells in the brains of primates with radiation-induced de novo glioblastoma multiforme

Irina A. Lubensky, Alexander O. Vortmeyer, Stephanie Kim, Russell R. Lonser, Deric M. Park, Barbara Ikejiri, Jie Li, Hiroaki Okamoto, Stuart Walbridge, Caroline Ryschkewitsch, Eugene Major, Edward H. Oldfield, Zhengping Zhuang

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The pathogenesis of de novo glioblastoma multiforme (GBM) is poorly understood and precursor cells are not known. To gain insight into the pathogenesis of GBM we analyzed brains from primates that developed de novo tumors ten years after whole brain radiation. Four animals had clinical and radiological evidence of GBM, and two animals had no evidence of GBM at the time of euthanization. Tumor precursor cells were identified diffusely scattered in the grossly normal white matter of all animals including two monkeys without evidence of GBM by MR-imaging or on autopsy examination. Tumor precursors demonstrated cellular atypia and mitoses, and were negative for tumor-associated markers GFAP, EGFR and p53. the cells were positive for Ki67 and N-CoR, the nuclear corepressor of astroglial differentiation. These results suggest that radiation-induced nuclear damage to neural stem cells or early astrocytic precursor cells can prevent normal differentiation and lead to tumor development. The findings provide insight into the tumorigenesis of de novo GBMs and suggest a new strategy for treatment of these lethal tumors by targeting both inactivation of N-CoR and inhibition of EGFR.

Original languageEnglish (US)
Pages (from-to)452-456
Number of pages5
JournalCell Cycle
Volume5
Issue number4
DOIs
StatePublished - Feb 16 2006
Externally publishedYes

Keywords

  • N-coR
  • Neural stem cell
  • Precursor cell
  • Primary glioblastoma multiforme
  • Radiation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Lubensky, I. A., Vortmeyer, A. O., Kim, S., Lonser, R. R., Park, D. M., Ikejiri, B., Li, J., Okamoto, H., Walbridge, S., Ryschkewitsch, C., Major, E., Oldfield, E. H., & Zhuang, Z. (2006). Identification of tumor precursor cells in the brains of primates with radiation-induced de novo glioblastoma multiforme. Cell Cycle, 5(4), 452-456. https://doi.org/10.4161/cc.5.4.2482