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gliomas

Thursday 27 November 2003

Gliomas account for >70% of all primary brain tumors. The most common (65%) and most malignant type is glioblastoma.

With the exception of pilocytic astrocytomas, the prognosis of glioma patients is still poor. Less than 3% of glioblastoma patients are still alive at 5 years after diagnosis, higher age being the most significant predictor of poor outcome.

Epidemiology

No underlying cause has been identified for the majority of malignant gliomas.

Epidemiologic factors including specific occupational exposures, environmental carcinogens, foods containing N-nitroso compounds, electromagnetic fields, etc. have been associated to only a small proportion of gliomas.

The only two firmly established factors of primary brain tumors are the exposure to high doses of ionizing radiation and inherited mutations of highly penetrant genes associated with rare syndromes (Table 3).

In addition, preliminary evidence points to a lower glioma risk among people with allergic conditions and high levels of serum IgE.

Polymorphisms of genes that affect detoxification, DNA repair, and cell-cycle regulation have also been implicated in the development of gliomas.

Types

- low-grade gliomas
- high-grade gliomas (malignant gliomas)

Classification

- astrocytic tumors

  • pilocytic astrocytoma
  • low-grade astrocytoma
  • anapalstic astrocytoma

- oligodendroglial tumors

  • oligodendrogliomas
    • low-grade oligodendroglioma/oligoastrocytoma
    • anaplastic oligodendroglioma/oligoastrocytoma

- glioblastoma multiforme (GBM)

Subtypes

- pediatric glial tumors (pediatric gliomas)

GWAS

Five risk loci for glioma (19578367) at
- 5p15.33 (rs2736100,
- TERT; P = 1.50 x 10(-17)),
- 8q24.21 (rs4295627, CCDC26; P = 2.34 x 10(-18)),
- 9p21.3 (rs4977756, CDKN2A-CDKN2B; P = 7.24 x 10(-15)),
- 20q13.33 (rs6010620, RTEL1; P = 2.52 x 10(-12))
- 11q23.3 (rs498872, PHLDB1; P = 1.07 x 10(-8)).

These data show that common low-penetrance susceptibility alleles contribute to the risk of developing glioma and provide insight into disease causation of this primary brain tumor. (19578367)

See also: gliomas (benign glioma/malignant glioma)

Cytogenetics

Allelotype (LOH)

1p36 LOH 15709179
14q LOH 20% 15164983
19q LOH 19q13 LOH 15709179

Reviews

- Yamanaka R. Cell- and peptide-based immunotherapeutic approaches for glioma. Trends Mol Med. 2008 May;14(5):228-35. PMID: 18403264

- Sanai N, Alvarez-Buylla A, Berger MS. Neural stem cells and the origin of gliomas. N Engl J Med. 2005 Aug 25;353(8):811-22. PMID: 16120861

- Konopka G, Bonni A. Signaling pathways regulating gliomagenesis. Curr Mol Med. 2003 Feb;3(1):73-84. PMID: 12558076

- Development of novel targeted therapies in the treatment of malignant glioma. Jeremy N. Rich & Darell D. Bigner Nature Reviews Drug Discovery 3, 430-446 (May 2004)

- Rao JS. Molecular mechanisms of glioma invasiveness: the role of proteases. Nat Rev Cancer. 2003 Jul;3(7):489-501.
PMID: 12835669

- Holland EC. Gliomagenesis: genetic alterations and mouse models. Nat Rev Genet. 2001 Feb;2(2):120-9. PMID: 11253051

References

- Genome-wide association study identifies five susceptibility loci for glioma. Shete S, Hosking FJ, Robertson LB, Dobbins SE, Sanson M, Malmer B, Simon M, Marie Y, Boisselier B, Delattre JY, Hoang-Xuan K, El Hallani S, Idbaih A, Zelenika D, Andersson U, Henriksson R, Bergenheim AT, Feychting M, Lönn S, Ahlbom A, Schramm J, Linnebank M, Hemminki K, Kumar R, Hepworth SJ, Price A, Armstrong G, Liu Y, Gu X, Yu R, Lau C, Schoemaker M, Muir K, Swerdlow A, Lathrop M, Bondy M, Houlston RS. Nat Genet. 2009 Aug;41(8):899-904. PMID: 19578367