KEGG   DISEASE: H00042Help
Entry
H00042                      Disease                                

Name
Glioma
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.
Category
Cancer
BRITE hierarchy
Pathway
Glioma
MicroRNAs in cancer
Gene
EGFR (amplification, 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]
Carcinogen
X- and gamma-radiation
Marker
p53 (mutation) [HSA:7157]
PTEN (mutation) [HSA:5728]
EGFR (amplification) [HSA:1956]
Drug
Carmustine [DR:D00254]
Lomustine [DR:D00363]
Procarbazine [DR:D00478]
Vincristine [DR:D02197]
Temozolomide [DR:D06067]
Comment
ICD-O: 9401/3, Tumor type: Anaplastic astrocytoma
ICD-O: 9440/3, Tumor type: Glioblastoma
Other DBs
ICD-10: 
MeSH: 
Reference
PMID:15639402 (gene, tumor type)
  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:11253051 (gene)
  Authors
Holland EC.
  Title
Gliomagenesis: genetic alterations and mouse models.
  Journal
Nat Rev Genet 2:120-9 (2001)
Reference
PMID:12154354 (gene)
  Authors
Zhu Y, Parada LF.
  Title
The molecular and genetic basis of neurological tumours.
  Journal
Nat Rev Cancer 2:616-26 (2002)
Reference
PMID:11604478 (carcinogen)
  Authors
Bondy ML, Wang LE, El-Zein R, de Andrade M, Selvan MS, Bruner JM, Levin VA, Alfred Yung WK, Adatto P, Wei Q.
  Title
Gamma-radiation sensitivity and risk of glioma.
  Journal
J Natl Cancer Inst 93:1553-7 (2001)
Reference
PMID:2790826 (carcinogen)
  Authors
Preston-Martin S, Mack W, Henderson BE.
  Title
Risk factors for gliomas and meningiomas in males in Los Angeles County.
  Journal
Cancer Res 49:6137-43 (1989)
Reference
PMID:12826827 (marker)
  Authors
Hill C, Hunter SB, Brat DJ.
  Title
Genetic markers in glioblastoma: prognostic significance and future therapeutic implications.
  Journal
Adv Anat Pathol 10:212-7 (2003)
Reference
(drug)
  Authors
Skeel RT (ed).
  Title
Handbook of Cancer Chemotherapy, Sixth Edition
  Journal
Lippincott Williams & Wilkins (2003)

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