Glioblastomas: Gliomagenesis, genetics, angiogenesis, and microenvironment

Background and purpose. - Glioblastomas are the most malignant gliomas of the central nervous system. Currently, numerous studies are attempting to decipher their genetic and epigenetic modifications, to identify the cells at the origin of gliomagenesis, and to better understand the molecular bases responsible for invasion and angiogenesis processes. Methods. - This article reviews recent data on the cellular and molecular biology of gliomas delineated by several teams including ours. We and others have underlined the role played by cancer stem cells in gliomagenesis; the Cancer Genome Atlas Network has described most glioblastoma genetic alterations. Results. - According to many studies, glioblastomas derive from malignant transformation of stem cells and/or glial precursor cells. Moreover, the topographic microenvironment is important regarding invasion and angiogenesis processes. Finally, it is now well established, thanks to IDH1 mutation identification, that primary and secondary glioblastomas are two different clinical and genetic entities. Interestingly, IDH1 mutation seems to be a very early genomic modification in astrocytoma, oligodendroglioma, and secondary glioblastoma tumorigenic processes. Conclusions. - Regarding all these data, we suggest a hypothetical model of glioma initiation, growth, and progression. Moreover, the histomolecular glioma classification has been substantially revised and new therapeutic targets have been identified. (C) 2010 Elsevier Masson SAS. All rights reserved.