KEGG   PATHWAY: hsa05214Help
Entry
hsa05214                    Pathway                                

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; Cancers
BRITE hierarchy
Pathway map
Glioma
hsa05214

All organismsOrtholog table
Disease
H00042  
Glioma
Organism
Homo sapiens (human) [GN:hsa]
Gene
1950  
EGF; epidermal growth factor [KO:K04357]
7039  
TGFA; transforming growth factor alpha [KO:K08774]
1956  
EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
5154  
PDGFA; platelet derived growth factor subunit A [KO:K04359]
5155  
PDGFB; platelet derived growth factor subunit B [KO:K17386]
5156  
PDGFRA; platelet derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
5159  
PDGFRB; platelet derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
3479  
IGF1; insulin like growth factor 1 [KO:K05459]
3480  
IGF1R; insulin like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
5335  
PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
5336  
PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
810  
CALML3; calmodulin like 3 [KO:K02183]
805  
CALM2; calmodulin 2 (phosphorylase kinase, delta) [KO:K02183]
808  
CALM3; calmodulin 3 (phosphorylase kinase, delta) [KO:K02183]
801  
CALM1; calmodulin 1 (phosphorylase kinase, delta) [KO:K02183]
163688  
CALML6; calmodulin like 6 [KO:K02183]
51806  
CALML5; calmodulin like 5 [KO:K02183]
815  
CAMK2A; calcium/calmodulin-dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
817  
CAMK2D; calcium/calmodulin-dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
816  
CAMK2B; calcium/calmodulin-dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
818  
CAMK2G; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
5578  
PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
5579  
PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
5582  
PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
6464  
SHC1; SHC (Src homology 2 domain containing) transforming protein 1 [KO:K06279]
25759  
SHC2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K17447]
53358  
SHC3; SHC (Src homology 2 domain containing) transforming protein 3 [KO:K17448]
399694  
SHC4; SHC (Src homology 2 domain containing) family member 4 [KO:K17449]
2885  
GRB2; growth factor receptor bound protein 2 [KO:K04364]
6654  
SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
6655  
SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
3265  
HRAS; Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845  
KRAS; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
4893  
NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
369  
ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
673  
BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
5894  
RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604  
MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  
MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
5290  
PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [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]
5291  
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294  
PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
5295  
PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
23533  
PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K02649]
5296  
PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  
PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
207  
AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
208  
AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
10000  
AKT3; v-akt murine thymoma viral oncogene homolog 3 [KO:K04456] [EC:2.7.11.1]
2475  
MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
5728  
PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.67 3.1.3.48 3.1.3.16]
1029  
CDKN2A; cyclin-dependent kinase inhibitor 2A [KO:K06621]
4193  
MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
7157  
TP53; tumor protein p53 [KO:K04451]
1026  
CDKN1A; cyclin-dependent kinase inhibitor 1A [KO:K06625]
595  
CCND1; cyclin D1 [KO:K04503]
1019  
CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
1021  
CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
5925  
RB1; retinoblastoma 1 [KO:K06618]
1869  
E2F1; E2F transcription factor 1 [KO:K17454]
1870  
E2F2; E2F transcription factor 2 [KO:K09389]
1871  
E2F3; E2F transcription factor 3 [KO:K06620]
Compound
C00076  
Calcium cation
C00165  
Diacylglycerol
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
J Clin Neurosci 12:1-5 (2005)
Reference
  Authors
Zhu Y, Parada LF.
  Title
The molecular and genetic basis of neurological tumours.
  Journal
Nat Rev Cancer 2:616-26 (2002)
Reference
  Authors
Holland EC.
  Title
Gliomagenesis: genetic alterations and mouse models.
  Journal
Nat Rev Genet 2:120-9 (2001)
Reference
  Authors
Bansal K, Liang ML, Rutka JT.
  Title
Molecular biology of human gliomas.
  Journal
Technol Cancer Res Treat 5:185-94 (2006)
Reference
(Japanese)
  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
Neurosurgery 52:1425-34; discussion 1434-5 (2003)
Reference
  Authors
Hulleman E, Helin K.
  Title
Molecular mechanisms in gliomagenesis.
  Journal
Adv Cancer Res 94:1-27 (2005)
Reference
  Authors
Schlessinger J.
  Title
Cell signaling by receptor tyrosine kinases.
  Journal
Cell 103:211-25 (2000)
Reference
PMID:9643506
  Authors
Ng HK, Lam PY.
  Title
The molecular genetics of central nervous system tumors.
  Journal
Pathology 30:196-202 (1998)
Reference
  Authors
Knobbe CB, Merlo A, Reifenberger G.
  Title
Pten signaling in gliomas.
  Journal
Neuro-oncol 4:196-211 (2002)
KO pathway
 

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