Table 1.
Molecular classifications of GB subtypes.
| Phillips et al. [106] | Verhaak et al. [5] | ||||||
|---|---|---|---|---|---|---|---|
| Classification | Proneural | Proliferative | Mesenchymal | Proneural | Neural | Mesenchymal | Classical |
| Tumor type | WHO grade III or IV with or without necrosis | WHO grade IV with necrosis | WHO grade IV with necrosis | GB | GB | GB | GB |
| Survival prognosis | Longer | Short | Short | Longer | Short | Short | Short |
| Treatment efficiency | ND | ND | ND | Non-effective | Effective | Effective | Effective |
| Chromosome gain/loss | None | 10q23.3 del (PTEN) 7p11.2 amp (EGFR) |
10q23.3 del (PTEN) 7p11.2 amp (EGFR) |
+7/−10 (54%) 4q12 amp (PDGFRA) |
- | 17q11.2 del (NF1) | +7/−10 9p21.3 del (CDKN2A) |
| EGFR | Normal | Amplified or normal | Amplified or normal | - | Amplified | - | Highly amplified, EGFRvIII |
| Mutations | - | - | - | IDH1, PDGFRA, TP53 | - | NF1 | EGFRvIII TP53 wildtype |
| Overexpressed genes | OLIG2, MAP2, DCX, ENC1, ERBB4, GAD2, DLL3, DLL1, HEY2, ASCL1 | PCNA, TOP2A | PECAM, VEGF, VEGFR1, VEGFR2 | PDGFRA, NKX2-2, OLIG2 | - | TRADD, RELB, TNFRSF1A, CD68, PTPRC, TNF, CHI3L1, MET, | NES, NOTCH3, JAG1, LFNG, SMO, GAS1, GLI2 |
| Markers | Markers specific to neuroblasts and immature neurons | MELK, EGFR | EGFR, VEGF, VEGFR1, VEGFR2, endothelial cell markers, CHI3L1, CD44, STAT3, vimentin |
SOX genes, DCX, DLL3, ASCL1, TCF4 | NEFL, GABRA1, SYT1, SLC12A5. Expression patterns similar to normal brain tissue |
CD44, MERTK | EGFR/EGFRvIII, TP53 wildtype |
ASCL1, Achaete-Scute Family BHLH Transcription Factor 1; amp, amplification; CDKN2A, cyclin-dependent kinase inhibitor 2A; CHI3L1, Chitinase 3-Like 1; DCX, Doublecortin; del, deletion; DLL1, Delta Like Canonical Notch Ligand 1; DLL3, Delta Like Canonical Notch Ligand 3; EGFR, epidermal growth factor receptor; EGFRvIII, epidermal growth factor receptor variant III; ENC1, Ectodermal-Neural Cortex 1; ERBB4, Erb-B2 Receptor Tyrosine Kinase 4; GABRA1, Gamma-Aminobutyric Acid Type A Receptor Subunit Alpha1; GAD2, Glutamate Decarboxylase 2; GAS1, Growth Arrest Specific 1; GB, Glioblastoma; GLI2, GLI Family Zinc Finger 2; HEY2, Hes Related Family BHLH Transcription Factor With YRPW Motif 2; IDH1, isocitrate dehydrogenase 1; JAG1, Jagged Canonical Notch Ligand 1; LFNG, Lunatic Fringe (Drosophila) Homolog; MAP2, Microtubule Associated Protein 2; MELK, Maternal Embryonic Leucine Zipper Kinase; MERTK, MET Proto-Oncogene, Receptor Tyrosine Kinase; ND, not determined; NEFL, Neurofilament Light Chain; NES, Nestin; NF1, neurofibromin 1; NKX2-2, Homeobox Protein NK-2 Homolog B; NOTCH3, Notch Receptor 3; OLIG2, Oligodendrocyte Transcription Factor 2; PCNA, Proliferating cell nuclear antigen; PDGFRA, platelet-derived growth factor receptor A; PECAM, Platelet endothelial cell adhesion molecule; PTEN, phosphatase and tensin homolog; PTPRC, Protein Tyrosine Phosphatase Receptor Type C; RELB, RELB Proto-Oncogene, NF-KB Subunit; SLC12A5, Solute Carrier Family 12 Member 5; SMO, Smoothened; SOX, SRY-Box Transcription Factor 2; STAT3, Signal Transducer and Activator Of Transcription 3; SYT1, Synaptotagmin 1; TCF4, Transcription Factor 4; TNF, tumor necrosis factor; TNFRSF1A, Tumor necrosis factor receptor superfamily member 1A; TOP2A, DNA Topoisomerase II Alpha; TP53, Tumor Protein P53; TRADD, Tumor necrosis factor receptor type 1-associated DEATH domain; VEGF, Vascular endothelial growth factor; VEGFR1, Vascular endothelial growth factor receptor 1; VEGFR2; Vascular endothelial growth factor receptor 2; WHO, World Health Organization.