Abstract
Glioblastoma (GBM) is highly invasive and the deadliest brain tumor in adults. It is characterized by inter-tumor and intra-tumor heterogeneity, short patient survival, and lack of effective treatment. Prognosis and therapy selection is driven by molecular data from gene transcription, genetic alterations and DNA methylation. The four GBM molecular subtypes are proneural, neural, classical, and mesenchymal. More effective personalized therapy heavily depends on higher resolution molecular subtype signatures, combined with gene therapy, immunotherapy and organoid technology. In this review, we summarize the principal GBM molecular classifications that guide diagnosis, prognosis, and therapeutic recommendations.
Highlights
The World Health Organization (WHO) defines adult diffuse gliomas into grade II and grade III astrocytic tumors, grade II and III oligodendrogliomas, and grade IV glioblastomas (Louis et al, 2016)
Proliferative and Mesenchymal subtypes are characterized by activation of PI3K/AKT (Phosphoinositide 3-kinase/Protein kinase B) signaling, loss on Chr.10, gain on Chr.7, and poor prognosis with invasive growth and angiogenic pathways (Phillips et al, 2006)
According to the characteristic of DNA methylation pattern causally related to IDH1/2 mutation status and better prognosis, the Proneural subtype is further subdivided into G-CIMP positive and negative groups (Noushmehr et al, 2010)
Summary
The World Health Organization (WHO) defines adult diffuse gliomas into grade II and grade III astrocytic tumors, grade II and III oligodendrogliomas, and grade IV glioblastomas (Louis et al, 2016). Initial Exploration on the Transcription-Based Classification In the 1990s, scientists acquired data from techniques like PCR, allele analysis, and first-generation sequencing to analyze gliomas They found a variety of molecular markers of different types and grades, but the landscape was not clear (Sehgal, 1998). Proliferative and Mesenchymal subtypes are characterized by activation of PI3K/AKT (Phosphoinositide 3-kinase/Protein kinase B) signaling, loss on Chr. (location of PTEN), gain on Chr. (location of EGFR), and poor prognosis with invasive growth and angiogenic pathways (Phillips et al, 2006) These three subtypes are reminiscent of the various stages of developmental neurogenesis, which provides the basis and perspective for the molecular classification of GBM. Sharma et al found that VEGF-A (Vascular endothelial growth factor A), VEGF-B (Vascular endothelial growth factor B), ANG1 (Angiopoietin 1) and ANG24 (Angiopoietin 24) genes are highly expressed in the Mesenchymal subtype (Sharma et al, 2017)
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