| Entry |
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| Name |
Glioma |
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| 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.
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| Category |
Cancer
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| Brite |
Human diseases [BR:br08402]
Cancers
Cancers of eye, brain, and central nervous system
H00042 Glioma
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
Neoplasms of brain or central nervous system
2A00 Primary neoplasms of brain
H00042 Glioma
Cancer-accociated carbohydrates [br08441.html]
H00042
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| Pathway |
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| Network |
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| Element |
| N00006 | Amplified EGFR to RAS-ERK signaling pathway |
| N00016 | PDGF-overexpression to RAS-ERK signaling pathway |
| N00018 | Amplified PDGFR to RAS-ERK signaling pathway |
| N00027 | Amplified EGFR to PLCG-CAMK signaling pathway |
| N00029 | Amplified PDGFR to PLCG-CAMK signaling pathway |
| N00035 | Amplified EGFR to PI3K signaling pathway |
| N00040 | Amplified PDGFR to PI3K signaling pathway |
| N00041 | EGFR-overexpression to RAS-ERK signaling pathway |
| N00042 | EGFR-overexpression to PI3K signaling pathway |
| N00051 | Deleted PTEN to PI3K signaling pathway |
| N00052 | Mutation-inactivated PTEN to PI3K signaling pathway |
| N00067 | Deleted p14(ARF) to p21-cell cycle G1/S |
| N00068 | Amplified MDM2 to p21-cell cycle G1/S |
| N00071 | Deleted p16(INK4a) to p16-cell cycle G1/S |
| N00072 | Amplified CDK4 to cell cycle G1/S |
| N00074 | Loss of RB1 to cell cycle G1/S |
| N00115 | Mutation-inactivated TP53 to transcription |
| N00513 | Mutation-activated EGFR to RAS-ERK signaling pathway |
| N00514 | Mutation-activated EGFR to PI3K signaling pathway |
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| Gene |
EGFR (amplification, mutation, overexpression) [HSA: 1956] [KO: K04361]
MDM2 (amplification, overexpression) [HSA: 4193] [KO: K06643]
PTEN (mutation) [HSA: 5728] [KO: K01110]
p16/INK4A (deletion) [HSA: 1029] [KO: K06621]
PDGF-A (overexpression) [HSA: 5154] [KO: K04359]
PDGF-B (overexpression) [HSA: 5155] [KO: K17386]
PDGFR-alpha (overexpression, amplification) [HSA: 5156] [KO: K04363]
PDGFR-beta (overexpression, amplification) [HSA: 5159] [KO: K05089]
CDK4 (amplification) [HSA: 1019] [KO: K02089]
p53 (mutation) [HSA: 7157] [KO: K04451]
RB1 (loss) [HSA: 5925] [KO: K06618]
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| Carcinogen |
X- and gamma-radiation
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| Drug |
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| Comment |
ICD-O: 9401/3, Tumor type: Anaplastic astrocytoma
ICD-O: 9440/3, Tumor type: Glioblastoma
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| Other DBs |
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| Reference |
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| Authors |
Soni D, King JA, Kaye AH, Hovens CM. |
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| Title |
Genetics of glioblastoma multiforme: mitogenic signaling and cell cycle pathways converge. |
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| Journal |
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| Reference |
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| Authors |
Holland EC. |
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| Title |
Gliomagenesis: genetic alterations and mouse models. |
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| Journal |
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| Reference |
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| Authors |
Gan HK, Cvrljevic AN, Johns TG |
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| Title |
The epidermal growth factor receptor variant III (EGFRvIII): where wild things are altered. |
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| Journal |
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| Reference |
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| Authors |
Zhu Y, Parada LF. |
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| Title |
The molecular and genetic basis of neurological tumours. |
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| Journal |
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| Reference |
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| Authors |
Bondy ML, Wang LE, El-Zein R, de Andrade M, Selvan MS, Bruner JM, Levin VA, Alfred Yung WK, Adatto P, Wei Q. |
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| Title |
Gamma-radiation sensitivity and risk of glioma. |
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| Journal |
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| Reference |
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| Authors |
Preston-Martin S, Mack W, Henderson BE. |
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| Title |
Risk factors for gliomas and meningiomas in males in Los Angeles County. |
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| Journal |
Cancer Res 49:6137-43 (1989) |
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| Reference |
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| Authors |
Hill C, Hunter SB, Brat DJ. |
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| Title |
Genetic markers in glioblastoma: prognostic significance and future therapeutic implications. |
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| Journal |
Adv Anat Pathol 10:212-7 (2003) |
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| LinkDB |
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