**2. Classification of GBM**

According to the WHO classification of brain tumors based on histopathological origin, GBM is a primary brain tumor of neuroepithelial, glial origin. Ranking of GBM in clinical and prognostic significance is within the highest grade IV. GBM could also be classified according to mode of occurrence, as it could be a result of progression from less malignant glial tumor (so-called secondary type) or it could occur de novo (primary type). Another specific type is pediatric GBM. The most common is primary type. Primary, secondary, and pediatric GBMs have their own specific genetic and epigenetic alterations occurring in their gliomagenesis (see **Figure 1**). As diagnosis of GBM presents with heterogeneity of altered genetic pathways evidenced by The Cancer Genome Atlas Research Network's study, classification based on gene expression profile distinguishes a classical, mesenchymal, proneural, and neural type of GBM. Classical type typically harbors no TP53 mutations, but very high rate of epidermal growth factor receptor (EGFR) mutations. This type has a slightly better survival. Mesenchy‐ mal type displays frequent mutations of neurofibromatosis gene 1 (NF1), TP53, and PTEN genes and aggressive anticancer therapy brings a significant increase in survival of these patients. Third, proneural subtype presents with highest mutation rate of TP53, PDGFRA, and isocitrate dehydrogenase (IDH) and usually affects younger adults. Last, neural type occurs more often in older population and contains several gene mutations at an average rate [4]. These classifications show high heterogeneity of genetic profile, aggressiveness, clinical characteristics, and expected prognosis of GBM patients with a strong need of definite uniform classification of subtypes leading to more specific treatment for each GBM subtype.

**Figure 1.** Genes involved in genesis of primary, secondary, and pediatric glioblastoma. \* Gain of function through am‐ plification or mutation; <sup>ǂ</sup> homozygous deletion or mutation.
