KEGG PATHWAY: hsa05214

PATHWAY: hsa05214

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

Pathway map

hsa05214

Glioma

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]
5155	PDGFB; platelet-derived growth factor beta polypeptide [KO:K04359]
5154	PDGFA; platelet-derived growth factor alpha polypeptide [KO:K04359]
5156	PDGFRA; platelet-derived growth factor receptor, alpha polypeptide [KO:K04363] [EC:2.7.10.1]
5159	PDGFRB; platelet-derived growth factor receptor, beta polypeptide [KO:K05089] [EC:2.7.10.1]
3479	IGF1; insulin-like growth factor 1 (somatomedin C) [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 (phosphatidylinositol-specific) [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:K02677] [EC:2.7.11.13]
5582	PRKCG; protein kinase C, gamma [KO:K02677] [EC:2.7.11.13]
25759	SHC2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K06279]
399694	SHC4; SHC (Src homology 2 domain containing) family, member 4 [KO:K06279]
53358	SHC3; SHC (Src homology 2 domain containing) transforming protein 3 [KO:K06279]
6464	SHC1; SHC (Src homology 2 domain containing) transforming protein 1 [KO:K06279]
2885	GRB2; growth factor receptor-bound protein 2 [KO:K04364]
6654	SOS1; son of sevenless homolog 1 (Drosophila) [KO:K03099]
6655	SOS2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
3265	HRAS; v-Ha-ras Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845	KRAS; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
4893	NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
369	ARAF; v-raf murine sarcoma 3611 viral oncogene homolog [KO:K08845] [EC:2.7.11.1]
673	BRAF; v-raf murine sarcoma viral oncogene homolog B1 [KO:K04365] [EC:2.7.11.1]
5894	RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [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 (alpha) [KO:K02649]
23533	PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
5296	PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
8503	PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [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 (protein kinase B, gamma) [KO:K04456] [EC:2.7.11.1]
2475	MTOR; mechanistic target of rapamycin (serine/threonine kinase) [KO:K07203]
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 oncogene, E3 ubiquitin protein ligase [KO:K06643] [EC:6.3.2.19]
7157	TP53; tumor protein p53 [KO:K04451]
1026	CDKN1A; cyclin-dependent kinase inhibitor 1A (p21, Cip1) [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:K06620]
1871	E2F3; E2F transcription factor 3 [KO:K06620]
1870	E2F2; E2F transcription factor 2 [KO:K09389]

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)

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)

Reference

PMID:11253051

Authors

Holland EC.

Title

Gliomagenesis: genetic alterations and mouse models.

Journal

Nat Rev Genet 2:120-9 (2001)

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)

Reference

(Japanese)

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)

Reference

PMID:16095998

Authors

Hulleman E, Helin K.

Title

Molecular mechanisms in gliomagenesis.

Journal

Adv Cancer Res 94:1-27 (2005)

Reference

PMID:11057895

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

PMID:12084351

Authors

Knobbe CB, Merlo A, Reifenberger G.

Title

Pten signaling in gliomas.

Journal

Neuro-oncol 4:196-211 (2002)

KO pathway

ko05214

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Ontology (3)   
   KEGG BRITE (3)   
Pathway (1)   
   BioSystems (1)   
Disease (1)   
   KEGG DISEASE (1)   
Genome (1)   
   KEGG GENOME (1)   
Gene (65)   
   KEGG GENES (65)   
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