Glioma

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.

Cancer

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]

X- and gamma-radiation

Carmustine [DR:D00254]
Temozolomide [DR:D06067]
Bevacizumab [DR:D06409]

ICD-O: 9401/3, Tumor type: Anaplastic astrocytoma
ICD-O: 9440/3, Tumor type: Glioblastoma

PMID:15639402 (gene, tumor type)

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)
DOI:10.1016/j.jocn.2004.04.001

PMID:11253051

Holland EC.

Gliomagenesis: genetic alterations and mouse models.

Nat Rev Genet 2:120-9 (2001)
DOI:10.1038/35052535

PMID:23777544

Gan HK, Cvrljevic AN, Johns TG

The epidermal growth factor receptor variant III (EGFRvIII): where wild things are altered.

FEBS J 280:5350-70 (2013)
DOI:10.1111/febs.12393

PMID:12154354

Zhu Y, Parada LF.

The molecular and genetic basis of neurological tumours.

Nat Rev Cancer 2:616-26 (2002)
DOI:10.1038/nrc866

PMID:11604478 (carcinogen)

Bondy ML, Wang LE, El-Zein R, de Andrade M, Selvan MS, Bruner JM, Levin VA, Alfred Yung WK, Adatto P, Wei Q.

Gamma-radiation sensitivity and risk of glioma.

J Natl Cancer Inst 93:1553-7 (2001)
DOI:10.1093/jnci/93.20.1553

PMID:2790826 (carcinogen)

Preston-Martin S, Mack W, Henderson BE.

Risk factors for gliomas and meningiomas in males in Los Angeles County.

Cancer Res 49:6137-43 (1989)

PMID:12826827 (marker)

Hill C, Hunter SB, Brat DJ.

Genetic markers in glioblastoma: prognostic significance and future therapeutic implications.

Adv Anat Pathol 10:212-7 (2003)