The genomic and epigenomic landscape of GB have been thoroughly described, and biological subgroups have emerged, defining three molecular subtypes based on gene expression profiling signatures: proneural, classical, and mesenchymal. Over the last two decades, extensive and comprehensive molecular profiling of GB has brought new insights into gliomagenesis. The exact mechanisms of glioblastoma oncogenesis are yet to be discovered. Despite an aggressive multimodal therapeutic approach, GB IDHwt is associated with a dismal prognosis, showing a median survival of 8 months and an overall 5-year relative survival rate of 5.5%. Īs opposed to astrocytoma IDH-mutant WHO grade 4 (formerly, GB, IDH-mutant), GB, IDHwt arises de novo (without preexisting precursor lesion) and typically manifests rapidly after a short clinical history. It belongs to the «adult-type diffuse glioma» family that also includes astrocytoma IDH-mutant (WHO grade 2, 3, or 4) and oligodendroglioma, IDH-mutant and 1p/19q-codeleted (WHO grade 2 or 3). It is classified as grade 4 in the World Health Organization (WHO) classification of tumors of the CNS. Glioblastoma (GB), IDH wild-type (wt) is the most common and aggressive form of glial tumors, accounting for almost 50% of primary malignant central nervous system (CNS) tumors. This review synthesizes the potential roles of mesenchymal stromal cells in the context of glioblastoma and provides novel research avenues to better understand this lethal disease. These fibroblast-like cells, which derive from the neural crest and reside in the perivascular niche, may underlie gliomagenesis and exert pro-tumoral effects within the tumor microenvironment. Mesenchymal stromal cells emerge as potential glioblastoma-initiating cells, especially with regard to the mesenchymal molecular subtype. However, the cellular origin of glioblastoma with mesenchymal molecular features remains elusive. These findings brought significant advancement to the comprehension of gliomagenesis. Recent studies have led to the hypothesis that glioblastoma arises from neural stem cells and glial precursor cells and that cell lineage constitutes a key determinant of the glioblastoma molecular subtype. The exact mechanisms of glioblastoma oncogenesis, including the identification of the glioma-initiating cell, are yet to be discovered. Glioblastoma, IDH wild-type is the most common and aggressive form of glial tumors.
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