Entry Name Glioma - Homo sapiens (human)
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 Network Element N00006 Amplified EGFR to RAS-ERK signaling pathway
N00016 PDGF-overexpression to RAS-ERK signaling pathway
N00018 Amplified PDGFR to RAS-ERK signaling pathway
N00027 Amplified EGFR to PLCG-CAMK signaling pathway
N00029 Amplified PDGFR to PLCG-CAMK signaling pathway
N00035 Amplified EGFR to PI3K signaling pathway
N00040 Amplified PDGFR to PI3K signaling pathway
N00041 EGFR-overexpression to RAS-ERK signaling pathway
N00042 EGFR-overexpression to PI3K signaling pathway
N00051 Deleted PTEN to PI3K signaling pathway
N00052 Mutation-inactivated PTEN to PI3K signaling pathway
N00067 Deleted p14(ARF) to p21-cell cycle G1/S
N00068 Amplified MDM2 to p21-cell cycle G1/S
N00071 Deleted p16(INK4a) to p16-cell cycle G1/S
N00072 Amplified CDK4 to cell cycle G1/S
N00074 Loss of RB1 to cell cycle G1/S
N00115 Mutation-inactivated TP53 to transcription
N00513 Mutation-activated EGFR to RAS-ERK signaling pathway
N00514 Mutation-activated EGFR to PI3K signaling pathway
Disease Drug D10024 Selumetinib sulfate (JAN/USAN)
Organism Homo sapiens (human) [GN:
hsa ]
Gene 1026 CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625 ]
1029 CDKN2A; cyclin dependent kinase inhibitor 2A [KO:K06621 ]
10912 GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402 ]
1643 DDB2; damage specific DNA binding protein 2 [KO:K10140 ]
1647 GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402 ]
2885 GRB2; growth factor receptor bound protein 2 [KO:K04364 ]
3265 HRAS; HRas proto-oncogene, GTPase [KO:K02833 ]
3479 IGF1; insulin like growth factor 1 [KO:K05459 ]
3845 KRAS; KRAS proto-oncogene, GTPase [KO:K07827 ]
4616 GADD45B; growth arrest and DNA damage inducible beta [KO:K04402 ]
4893 NRAS; NRAS proto-oncogene, GTPase [KO:K07828 ]
5154 PDGFA; platelet derived growth factor subunit A [KO:K04359 ]
5155 PDGFB; platelet derived growth factor subunit B [KO:K17386 ]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
578 BAK1; BCL2 antagonist/killer 1 [KO:K14021 ]
581 BAX; BCL2 associated X, apoptosis regulator [KO:K02159 ]
5925 RB1; RB transcriptional corepressor 1 [KO:K06618 ]
6654 SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
6655 SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
7039 TGFA; transforming growth factor alpha [KO:K08774 ]
815 CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515 ] [EC:2.7.11.17 ]
816 CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515 ] [EC:2.7.11.17 ]
817 CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515 ] [EC:2.7.11.17 ]
818 CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515 ] [EC:2.7.11.17 ]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
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 hsa04060 Cytokine-cytokine receptor interaction
KO pathway
