Contribution of tumor heterogeneity in a new animal model of CNS tumors.

Abstract

UNLABELLED:

The etiology of central nervous system (CNS) tumor heterogeneity is unclear. To clarify this issue, a novel animal model was developed of glioma and atypical teratoid/rhabdoid-like tumor (ATRT) produced in rats by nonviral cellular transgenesis initiated in utero. This model system affords the opportunity for directed oncogene expression, clonal labeling, and addition of tumor-modifying transgenes. By directing HRasV12 and AKT transgene expression in different cell populations with promoters that are active ubiquitously (CAG promoter), astrocyte-selective (glial fibrillary acidic protein promoter), or oligodendrocyte-selective (myelin basic protein promoter) we generated glioblastoma multiforme and anaplastic oligoastrocytoma, respectively. Importantly, the glioblastoma multiforme and anaplastic oligoastrocytoma tumors were distinguishable at both the cellular and molecular level. Furthermore, proneural basic helix-loop-helix (bHLH) transcription factors, Ngn2 (NEUROG2) or NeuroD1, were expressed along with HRasV12 and AKT in neocortical radial glia, leading to the formation of highly lethal ATRT like tumors. This study establishes a unique model in which determinants of CNS tumor diversity can be parsed out and reveals that both mutation and expression of neurogenic bHLH transcription factors contribute to CNS tumor diversity.

IMPLICATIONS:

A novel CNS tumor model reveals that oncogenic events occurring in disparate cell types and/or molecular contexts lead to different tumor types; these findings shed light on the sources of brain tumor heterogeneity.

• Authors: Fuyi Chen, Albert J Becker, Joseph J LoTurco
• Journal: Molecular cancer research : MCR (Mol Cancer Res) Vol. 12 Issue 5 Pg. 742-53 (May 2014) ISSN: 1557-3125 [Electronic] United States
• PMID: 24501428 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: ©2014 AACR.

Topics

• Animals
• Brain Neoplasms (genetics, pathology)
• Cells, Cultured
• Disease Models, Animal
• Female
• Glioblastoma (genetics, pathology)
• Mice
• Pregnancy
• Rats
• Rats, Wistar