KEGG   PATHWAY: oas05214
Entry
oas05214                    Pathway                                
Name
Glioma - Ovis aries (sheep)
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 types
Pathway map
oas05214  Glioma
oas05214

Organism
Ovis aries (sheep) [GN:oas]
Gene
101106508  TGFA; protransforming growth factor alpha isoform X2 [KO:K08774]
780479  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
114110564  PDGFA; platelet-derived growth factor subunit A isoform X2 [KO:K04359]
443545  PDGFB; platelet-derived growth factor subunit B precursor [KO:K17386]
101106012  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
101122783  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
443318  IGF1; insulin-like growth factor I precursor [KO:K05459]
443515  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
101103341  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
101122126  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
101105840  calmodulin [KO:K02183]
443230  CALM2; calmodulin [KO:K02183]
105614854  calmodulin-alpha [KO:K02183]
101116338  CALM3; calmodulin-3 [KO:K02183]
101115216  CALM1; calmodulin-1 isoform X2 [KO:K02183]
100037684  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
121820456  calmodulin-1-like [KO:K02183]
101123572  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
101103762  CAMK1; calcium/calmodulin-dependent protein kinase type 1 isoform X2 [KO:K08794] [EC:2.7.11.17]
101108939  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:2.7.11.17]
101105428  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G isoform X2 [KO:K08794] [EC:2.7.11.17]
443453  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101113850  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X4 [KO:K04515] [EC:2.7.11.17]
101108884  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X10 [KO:K04515] [EC:2.7.11.17]
101118870  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
101108308  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X2 [KO:K05869] [EC:2.7.11.17]
101110074  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101118410  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101116423  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
101113548  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
101113847  SHC2; SHC-transforming protein 2 [KO:K17447]
101107936  SHC3; SHC-transforming protein 3 [KO:K17448]
101110241  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
101109893  GRB2; growth factor receptor-bound protein 2 isoform X5 [KO:K04364]
114110058  growth factor receptor-bound protein 2 [KO:K04364]
101118865  SOS1; son of sevenless homolog 1 isoform X2 [KO:K03099]
101102732  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
101104357  HRAS; GTPase HRas isoform X1 [KO:K02833]
114114919  GTPase HRas-like [KO:K02833]
101114005  KRAS; GTPase KRas isoform X1 [KO:K07827]
101102438  NRAS; GTPase NRas [KO:K07828]
100305131  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
101107438  BRAF; serine/threonine-protein kinase B-raf isoform X3 [KO:K04365] [EC:2.7.11.1]
101103190  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
101123635  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
101113846  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
101115485  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
101123008  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101109759  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101110015  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101117348  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922] [EC:2.7.1.153]
101123247  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101111546  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649]
101121455  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
101118462  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101119242  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100294652  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100271659  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
101119351  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X2 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
114113021  cyclin-dependent kinase inhibitor 2A [KO:K06621]
101104979  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
101103187  E3 ubiquitin-protein ligase Mdm2-like [KO:K06643] [EC:2.3.2.27]
443421  TP53; cellular tumor antigen p53 [KO:K04451]
100302083  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100144763  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100144756  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
100144761  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
100144755  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
101117526  E2F1; transcription factor E2F1 [KO:K17454]
105606975  E2F2; transcription factor E2F2 [KO:K09389]
101121809  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
101115240  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
100885762  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101120573  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
443059  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
443062  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
101116344  DDB2; DNA damage-binding protein 2 isoform X2 [KO:K10140]
101109360  POLK; DNA polymerase kappa isoform X1 [KO:K03511] [EC:2.7.7.7]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:15639402
  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)
DOI:10.1016/j.jocn.2004.04.001
Reference
PMID:12154354
  Authors
Zhu Y, Parada LF.
  Title
The molecular and genetic basis of neurological tumours.
  Journal
Nat Rev Cancer 2:616-26 (2002)
DOI:10.1038/nrc866
Reference
PMID:11253051
  Authors
Holland EC.
  Title
Gliomagenesis: genetic alterations and mouse models.
  Journal
Nat Rev Genet 2:120-9 (2001)
DOI:10.1038/35052535
Reference
PMID:16700615
  Authors
Bansal K, Liang ML, Rutka JT.
  Title
Molecular biology of human gliomas.
  Journal
Technol Cancer Res Treat 5:185-94 (2006)
DOI:10.1177/153303460600500302
Reference
  Authors
Tabuchi K (ed).
  Title
[Gliomas: Research and therapy] (In Japanese)
  Journal
Springer-Verlag Tokyo (2006)
Reference
PMID:12762887
  Authors
Kapoor GS, O'Rourke DM.
  Title
Mitogenic signaling cascades in glial tumors.
  Journal
Neurosurgery 52:1425-34; discussion 1434-5 (2003)
DOI:10.1227/01.NEU.0000065135.28143.39
Reference
PMID:16095998
  Authors
Hulleman E, Helin K.
  Title
Molecular mechanisms in gliomagenesis.
  Journal
Adv Cancer Res 94:1-27 (2005)
DOI:10.1016/S0065-230X(05)94001-3
Reference
PMID:11057895
  Authors
Schlessinger J.
  Title
Cell signaling by receptor tyrosine kinases.
  Journal
Cell 103:211-25 (2000)
DOI:10.1016/S0092-8674(00)00114-8
Reference
PMID:9643506
  Authors
Ng HK, Lam PY.
  Title
The molecular genetics of central nervous system tumors.
  Journal
Pathology 30:196-202 (1998)
DOI:10.1080/00313029800169236
Reference
PMID:12084351
  Authors
Knobbe CB, Merlo A, Reifenberger G.
  Title
Pten signaling in gliomas.
  Journal
Neuro-oncol 4:196-211 (2002)
DOI:10.1093/neuonc/4.3.196
Related
pathway
oas04010  MAPK signaling pathway
oas04012  ErbB signaling pathway
oas04020  Calcium signaling pathway
oas04060  Cytokine-cytokine receptor interaction
oas04110  Cell cycle
oas04115  p53 signaling pathway
oas04150  mTOR signaling pathway
KO pathway
ko05214   
LinkDB

DBGET integrated database retrieval system