Abstract 359: Systematic manipulation of brain tumor diversity using piggybac transposon mediated transgenesis approach in rat.

Abstract

Abstract Animal models are important for interrogating the native biology of tumor formation, invasiveness, and may lead to novel therapeutic approaches. Here we describe the development of a rat glioma model which provides a fast and convenient approach to reproducibly induce brain tumors of different type in rat. We utilize a piggybac transposon system delivered by in utero electroporation (PB-IUE) to express oncogenic HRasV12 in different cell types in CNS. When expression of HRasV12 was driven by ubiquitous CAG promoter in radial glia cells, glioblastoma multiforme (GBM) was induced. When we specifically express HRasV12 in astrocytes using a mouse GFAP promoter, malignant astroglioma resembling GBM was induced in rat brains. In contrast, anaplastic oligoastrocytoma was induced when HRasV12 were expressed in oligodendrocytes under the control a rat MBP promoter. Surprisingly when co-expressing a basic helix loop helix protein Neurogenin2 (Ngn2) with HRasV12 both driven by CAG promoter, primitive neuroectodermal tumor (PNET) like tumors were generated. Molecular classification of tumors induced by CAG and GFAP HRasV12 matched mesenchymal GBM subtypes. Our data demonstrate the induction of different tumor types using a non-viral piggyBac transposon mediated transgenesis approach. The binary plasmid system we developed provides a method to direct different oncogenetic signals to different cell types. The models generated with this system should facilitate our understanding of the sources of tumor diversity. Citation Format: Fuyi Chen, Albert Becker, Joseph LoTurco. Systematic manipulation of brain tumor diversity using piggybac transposon mediated transgenesis approach in rat. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 359. doi:10.1158/1538-7445.AM2013-359