Published online Jan 26, 2014. doi: 10.4252/wjsc.v6.i1.43
Revised: November 6, 2013
Accepted: December 12, 2013
Published online: January 26, 2014
Glioma incidence rates in the United States are near 20000 new cases per year, with a median survival time of 14.6 mo for high-grade gliomas due to limited therapeutic options. The origins of these tumors and their many subtypes remain a matter of investigation. Evidence from mouse models of glioma and human clinical data have provided clues about the cell types and initiating oncogenic mutations that drive gliomagenesis, a topic we review here. There has been mixed evidence as to whether or not the cells of origin are neural stem cells, progenitor cells or differentiated progeny. Many of the existing murine models target cell populations defined by lineage-specific promoters or employ lineage-tracing methods to track the potential cells of origin. Our ability to target specific cell populations will likely increase concurrently with the knowledge gleaned from an understanding of neurogenesis in the adult brain. The cell of origin is one variable in tumorigenesis, as oncogenes or tumor suppressor genes may differentially transform the neuroglial cell types. Knowledge of key driver mutations and susceptible cell types will allow us to understand cancer biology from a developmental standpoint and enable early interventional strategies and biomarker discovery.
Core tip: The origins of glioma are not well understood. We approach the topic by review of our knowledge concerning the different cell types found in the mammalian brain, we describe mouse models aiming to model gliomagenesis and highlight relevant clinical data. Our aim is to integrate these three areas to provide a comprehensive snapshot of progress made towards the discovery of the process driving glioma formation.