Brain, Journal Year: 2019, Volume and Issue: 142(4), P. 847 - 866

Published: March 21, 2019

The complexity of glioblastoma multiforme, the most common and lethal variant gliomas, is reflected by cellular molecular heterogeneity at both inter- intra-tumoural levels. Molecular subtyping has arisen in past two decades as a promising strategy to give better predictions multiforme evolution, disease pathways, rational treatment options. Cancer Genome Atlas network initially identified four subtypes multiforme: proneural, neural, mesenchymal classical. However, further studies, also investigated glioma stem cells, have only three subtypes: proneural-mesenchymal transition upon tumour recurrence been suggested mechanism resistance radiation chemotherapy treatment. Glioblastoma patients with subtype tend survive shorter than other when analysis restricted samples low transcriptional heterogeneity. Although signature malignant may seem odds idea ectodermal origin neural-glial lineages, presence supported several studies suggesting that it can result from: (i) intrinsic expression cells affected accumulated genetic mutations cell origin; (ii) micro-environments recruited macrophages or microglia, pericytes, progenitors; (iii) treatment, including radiotherapy, antiangiogenic therapy possibly chemotherapy. Genetic abnormalities, mainly NF1 mutations, together NF-κB programs, are main driver acquiring mesenchymal-signature. This far from being simply tissue artefacts, single glioma, circulating released micro-environment. All these suggest induced sustained via mechanisms micro-environment factors. poorer prognosis, they favourable response immunotherapy intensive radio-

Language: Английский