[Glioblastomas: gliomagenesis, genetics, angiogenesis, and microenvironment].
OBJECTIVE
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.
Figarella-Branger
D
D
Inserm U911, faculté de médecine Timone, 27, boulevard Jean-Moulin, 13285 Marseille cedex 05, France. dominique.ﬁgarella-branger@univmed.fr
Colin
C
C
Tchoghandjian
A
A
Baeza
N
N
Bouvier
C
C
D001932:Brain Neoplasms / Q000098:blood supply / Q000209:etiology / Q000235:genetics; D005909:Glioblastoma / Q000098:blood supply / Q000209:etiology / Q000235:genetics; D006801:Humans; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells; D009389:Neovascularization, Pathologic; D059016:Tumor Microenvironment