KEGG   PATHWAY: ptr05214
Entry
ptr05214                    Pathway                                
Name
Glioma - Pan troglodytes (chimpanzee)
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
ptr05214  Glioma
ptr05214

Organism
Pan troglodytes (chimpanzee) [GN:ptr]
Gene
461435  EGF; pro-epidermal growth factor isoform X3 [KO:K04357]
463415  EGFR; epidermal growth factor receptor isoform X2 [KO:K04361] [EC:2.7.10.1]
740202  PDGFA; platelet-derived growth factor subunit A isoform X2 [KO:K04359]
458844  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
461318  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
462188  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
741055  IGF1; insulin-like growth factor I isoform X6 [KO:K05459]
453676  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
458253  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
454268  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
737566  CALML5; calmodulin-like protein 5 [KO:K02183]
466008  CALML3; calmodulin-like protein 3 [KO:K02183]
459213  CALM2; calmodulin-2 [KO:K02183]
738819  CALM1; calmodulin-1 [KO:K02183]
456153  CALM3; calmodulin-3 [KO:K02183]
743250  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
453534  CALML4; calmodulin-like protein 4 isoform X2 [KO:K02183]
460153  CAMK1; calcium/calmodulin-dependent protein kinase type 1 isoform X2 [KO:K08794] [EC:2.7.11.17]
469667  CAMK1G; calcium/calmodulin-dependent protein kinase type 1G [KO:K08794] [EC:2.7.11.17]
450308  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:2.7.11.17]
461445  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X14 [KO:K04515] [EC:2.7.11.17]
462189  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
738330  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
738167  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
461992  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X2 [KO:K05869] [EC:2.7.11.17]
454832  PRKCA; protein kinase C alpha type isoform X2 [KO:K02677] [EC:2.7.11.13]
453993  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
456276  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
457351  SHC1; SHC-transforming protein 1 isoform X7 [KO:K06279]
749831  SHC2; LOW QUALITY PROTEIN: SHC-transforming protein 2 [KO:K17447]
450176  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
453414  SHC4; SHC-transforming protein 4 [KO:K17449]
737245  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
459171  SOS1; son of sevenless homolog 1 isoform X2 [KO:K03099]
452897  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
466302  HRAS; GTPase HRas isoform X1 [KO:K02833]
473387  KRAS; GTPase KRas isoform X1 [KO:K07827]
742713  NRAS; GTPase NRas [KO:K07828]
100614256  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
463781  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
460182  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
450188  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
456390  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
454037  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
458680  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
460858  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
457922  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
471079  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
456565  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
461836  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
455855  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
456035  AKT2; RAC-beta serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
740898  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100609583  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
457945  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
466142  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
465021  CDKN2A; cyclin-dependent kinase inhibitor 2A [KO:K06621]
742141  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
455214  TP53; cellular tumor antigen p53 isoform X2 [KO:K04451]
104001067  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
747442  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
452025  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
746968  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
452715  RB1; retinoblastoma-associated protein isoform X2 [KO:K06618]
107969994  E2F1; transcription factor E2F1 [KO:K17454]
469153  E2F2; transcription factor E2F2 isoform X2 [KO:K09389]
471865  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
464585  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
744311  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
456929  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X2 [KO:K04402]
747093  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
462616  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
451165  DDB2; DNA damage-binding protein 2 isoform X2 [KO:K10140]
461803  POLK; DNA polymerase kappa isoform X3 [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
ptr04010  MAPK signaling pathway
ptr04012  ErbB signaling pathway
ptr04020  Calcium signaling pathway
ptr04060  Cytokine-cytokine receptor interaction
ptr04110  Cell cycle
ptr04115  p53 signaling pathway
ptr04150  mTOR signaling pathway
KO pathway
ko05214   
LinkDB

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