Entry Name Glioma
Description Gliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (astrocytomas), oligodendrocytes (oligodendrogliomas), mixtures of various glial cells (for example,oligoastrocytomas) and ependymal cells (ependymomas). The most malignant form of infiltrating astrocytoma - glioblastoma multiforme (GBM) - is one of the most aggressive human cancers. GBM may develop de novo (primary glioblastoma) or by progression from low-grade or anaplastic astrocytoma (secondary glioblastoma). Primary glioblastomas develop in older patients and typically show genetic alterations (EGFR amplification, p16/INK4a deletion, and PTEN mutations) at frequencies of 24-34%. Secondary glioblastomas develop in younger patients and frequently show overexpression of PDGF and CDK4 as well as p53 mutations (65%) and loss of Rb playing major roles in such transformations. Loss of PTEN has been implicated in both pathways, although it is much more common in the pathogenesis of primary GBM.
Class Human Diseases; Cancer: specific typesBRITE hierarchy
Pathway map Disease Orthology K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K01116 PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11 ]
K02159 BAX; apoptosis regulator BAX
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04357 EGF; epidermal growth factor
K04359 PDGFA; platelet-derived growth factor subunit A
K04363 PDGFRA, CD140A; platelet-derived growth factor receptor alpha [EC:2.7.10.1 ]
K04364 GRB2; growth factor receptor-bound protein 2
K04365 BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04402 GADD45; growth arrest and DNA-damage-inducible protein
K04451 TP53, P53; tumor protein p53
K04503 CCND1; G1/S-specific cyclin-D1
K04515 CAMK2; calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17 ]
K05087 IGF1R, CD221; insulin-like growth factor 1 receptor [EC:2.7.10.1 ]
K05089 PDGFRB, CD140B; platelet-derived growth factor receptor beta [EC:2.7.10.1 ]
K05459 IGF1; insulin-like growth factor 1
K05859 PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11 ]
K05869 CAMK4; calcium/calmodulin-dependent protein kinase IV [EC:2.7.11.17 ]
K06279 SHC1; SHC-transforming protein 1
K06618 RB1; retinoblastoma-associated protein
K06620 E2F3; transcription factor E2F3
K06621 CDKN2A, P16, INK4A; cyclin-dependent kinase inhibitor 2A
K06625 CDKN1A, P21, CIP1; cyclin-dependent kinase inhibitor 1A
K07203 MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1 ]
K07827 KRAS, KRAS2; GTPase KRas
K08774 TGFA; transforming growth factor, alpha
K08845 ARAF, ARAF1; A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K09389 E2F2; transcription factor E2F2
K10140 DDB2; DNA damage-binding protein 2
K14021 BAK, BAK1; Bcl-2 homologous antagonist/killer
K17386 PDGFB; platelet-derived growth factor subunit B
K17447 SHC2; SHC-transforming protein 2
K17448 SHC3; SHC-transforming protein 3
K17449 SHC4; SHC-transforming protein 4
K17454 E2F1; transcription factor E2F1
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Soni D, King JA, Kaye AH, Hovens CM.
Title Genetics of glioblastoma multiforme: mitogenic signaling and cell cycle pathways converge.
Journal Reference Authors Zhu Y, Parada LF.
Title The molecular and genetic basis of neurological tumours.
Journal Reference Authors Holland EC.
Title Gliomagenesis: genetic alterations and mouse models.
Journal Reference Authors Bansal K, Liang ML, Rutka JT.
Title Molecular biology of human gliomas.
Journal Reference Authors Tabuchi K (ed).
Title [Gliomas: Research and therapy] (In Japanese)
Journal Springer-Verlag Tokyo (2006)
Reference Authors Kapoor GS, O'Rourke DM.
Title Mitogenic signaling cascades in glial tumors.
Journal Reference Authors Hulleman E, Helin K.
Title Molecular mechanisms in gliomagenesis.
Journal Reference Authors Schlessinger J.
Title Cell signaling by receptor tyrosine kinases.
Journal Reference Authors Ng HK, Lam PY.
Title The molecular genetics of central nervous system tumors.
Journal Reference Authors Knobbe CB, Merlo A, Reifenberger G.
Title Pten signaling in gliomas.
Journal Related ko04060 Cytokine-cytokine receptor interaction
