stem cells share some resemblance with neural progenitor cells, both expressing the surface receptor CD133. CD44 can also be used as a cancer stem cell marker in a subset of glioblastoma tumour cells. Glioblastoma cancer stem cells appear to exhibit enhanced resistance to radiotherapy and chemotherapy mediated, at least in part, by up-regulation of the DNA damage response. Metabolism The IDH1 gene encodes for the enzyme isocitrate dehydrogenase 1 and is uncommonly mutated in glioblastoma (primary GBM: 5%, secondary GBM >80%). By producing very high concentrations of the oncometabolite D-2-hydroxyglutarate and dysregulating the function of the wild-type IDH1 enzyme, it induces profound changes to the metabolism of IDH1-mutated glioblastoma, compared with IDH1 wild-type glioblastoma or healthy astrocytes. Among others, it increases the glioblastoma cells' dependence on glutamine or glutamate as an energy source. IDH1-mutated glioblastomas are thought to have a very high demand for glutamate and use this amino acid and neurotransmitter as a chemotactic signal. Since healthy astrocytes excrete glutamate, IDH1-mutated glioblastoma cells do not favor dense tumor structures, but instead migrate, invade, and disperse into healthy parts of the brain where glutamate concentrations are higher. This may explain the invasive behavior of these IDH1-mutated glioblastoma. Ion channels Furthermore, GBM exhibits numerous alterations in genes that encode for ion channels, including upregulation of gBK potassium channels and ClC-3 chloride channels. By upregulating these ion channels, glioblastoma tumor cells are hypothesized to facilitate increased ion movement over the cell membrane, thereby increasing H2O movement through osmosis, which aids glioblastoma cells in changing cellular volume very rapidly. This is helpful in their extremely aggressive invasive behavior because quick adaptations in cellular volume can facilitate movement through the sinuous extracellular matrix of the brain. MicroRNA As of 2012, RNA interference, usually microRNA, was under investigation in tissue culture, pathology specimens, and preclinical animal models of glioblastoma. Additionally, experimental observations suggest that microRNA-451 is a key regulator of LKB1/AMPK signaling in cultured glioma cells and that miRNA clustering controls epigenetic pathways in the disease. Tumor vasculature GBM is characterized by abnormal vessels that present disrupted morphology and functionality. The high permeability and poor perfusion of the vasculature result in a disorganized blood flow within the tumor and can lead to increased hypoxia, which in turn facilitates cancer progression by promoting processes such as immunosuppression. Diagnosis When viewed with MRI, glioblastomas often appear as ring-enhancing lesions. The appearance is not specific, however, as other