KEGG   PATHWAY: aml05214
aml05214                    Pathway                                

Glioma - Ailuropoda melanoleuca (giant panda)
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.
Human Diseases; Cancer: specific types
Pathway map
aml05214  Glioma

Ailuropoda melanoleuca (giant panda) [GN:aml]
100467733  pro-epidermal growth factor isoform X1 [KO:K04357]
100467724  TGFA; protransforming growth factor alpha isoform X3 [KO:K08774]
100473486  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
100475543  PDGFB; platelet-derived growth factor subunit B isoform X4 [KO:K17386]
100464991  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:]
100472005  PDGFRB; LOW QUALITY PROTEIN: platelet-derived growth factor receptor beta [KO:K05089] [EC:]
100473254  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
100471374  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:]
100480586  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116] [EC:]
100481994  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:]
100478600  CALML6; calmodulin-like protein 6 [KO:K02183]
100470909  CALM2; calmodulin-2 [KO:K02183]
100484519  calmodulin [KO:K02183]
100484770  calmodulin-like protein 3 [KO:K02183]
100481177  CALM1; calmodulin-1 [KO:K02183]
100472122  CALM3; calmodulin-3 [KO:K02183]
100478732  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
100471632  CAMK1; calcium/calmodulin-dependent protein kinase type 1 isoform X1 [KO:K08794] [EC:]
100477852  CAMK1D; calcium/calmodulin-dependent protein kinase type 1D isoform X1 [KO:K08794] [EC:]
100475467  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X2 [KO:K04515] [EC:]
100466256  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X5 [KO:K04515] [EC:]
100474459  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X3 [KO:K04515] [EC:]
100478243  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:]
100473015  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:]
100477326  PRKCA; protein kinase C alpha type [KO:K02677] [EC:]
100478007  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:]
100484719  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:]
100480856  SHC1; SHC-transforming protein 1 isoform X2 [KO:K06279]
100480694  SHC2; LOW QUALITY PROTEIN: SHC-transforming protein 2 [KO:K17447]
100468080  SHC3; SHC-transforming protein 3 [KO:K17448]
100475137  SHC4; SHC-transforming protein 4 isoform X2 [KO:K17449]
100468916  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
100474396  SOS2; son of sevenless homolog 2 isoform X9 [KO:K03099]
100482526  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
100473836  HRAS; GTPase HRas isoform X1 [KO:K02833]
100483919  KRAS; GTPase KRas isoform X1 [KO:K07827]
100464196  NRAS; GTPase NRas [KO:K07828]
100475955  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:]
100469346  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:]
100482255  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:]
100478039  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
100465700  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
100470035  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
100472388  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
100463775  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:]
100479294  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
100479580  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:]
100475291  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100483828  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100467916  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100468763  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:]
100480414  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
100465793  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
100471122  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:]
100469483  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X2 [KO:K01110] [EC:]
100472171  cyclin-dependent kinase inhibitor 2A isoform X3 [KO:K06621]
100479481  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:]
100468516  TP53; cellular tumor antigen p53 [KO:K04451]
100484923  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100469787  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
100481236  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:]
100476389  CDK6; cyclin-dependent kinase 6 isoform X2 [KO:K02091] [EC:]
100477714  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
100475779  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
100484544  E2F3; transcription factor E2F3 [KO:K06620]
100477654  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha isoform X1 [KO:K04402]
100482871  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
100470600  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
100471095  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
100472241  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
100479738  DDB2; DNA damage-binding protein 2 isoform X1 [KO:K10140]
100464732  POLK; DNA polymerase kappa isoform X2 [KO:K03511] [EC:]
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Soni D, King JA, Kaye AH, Hovens CM.
Genetics of glioblastoma multiforme: mitogenic signaling and cell cycle pathways converge.
J Clin Neurosci 12:1-5 (2005)
Zhu Y, Parada LF.
The molecular and genetic basis of neurological tumours.
Nat Rev Cancer 2:616-26 (2002)
Holland EC.
Gliomagenesis: genetic alterations and mouse models.
Nat Rev Genet 2:120-9 (2001)
Bansal K, Liang ML, Rutka JT.
Molecular biology of human gliomas.
Technol Cancer Res Treat 5:185-94 (2006)
Tabuchi K (ed).
[Gliomas: Research and therapy] (In Japanese)
Springer-Verlag Tokyo (2006)
Kapoor GS, O'Rourke DM.
Mitogenic signaling cascades in glial tumors.
Neurosurgery 52:1425-34; discussion 1434-5 (2003)
Hulleman E, Helin K.
Molecular mechanisms in gliomagenesis.
Adv Cancer Res 94:1-27 (2005)
Schlessinger J.
Cell signaling by receptor tyrosine kinases.
Cell 103:211-25 (2000)
Ng HK, Lam PY.
The molecular genetics of central nervous system tumors.
Pathology 30:196-202 (1998)
Knobbe CB, Merlo A, Reifenberger G.
Pten signaling in gliomas.
Neuro-oncol 4:196-211 (2002)
aml04010  MAPK signaling pathway
aml04012  ErbB signaling pathway
aml04020  Calcium signaling pathway
aml04060  Cytokine-cytokine receptor interaction
aml04110  Cell cycle
aml04115  p53 signaling pathway
aml04150  mTOR signaling pathway
KO pathway

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