Brain Tumours

Giselle Y López, Duke University Medical Center, Durham, North Carolina, USA
Thomas J Cummings, Duke University Medical Center, Durham, North Carolina, USA
Darell D Bigner, Duke University Medical Center, Durham, North Carolina, USA
Roger E McLendon, Duke University Medical Center, Durham, North Carolina, USA

Published online: March 2011

DOI: 10.1002/9780470015902.a0006111.pub2

Brain tumour genetics allow for improved classification and development of therapeutic options for certain primary brain tumours. Tumours with specific genetic alterations and molecular profiles are also associated with certain inherited familial cancer syndromes, including Li–Fraumeni syndrome, neurofibromatosis and tuberous sclerosis. Recent advances in genetic profiling, from karyotype analyses to fluorescence in situ hybridisation (FISH) to genome-wide sequencing have greatly improved the understanding of the genetic basis for these tumours. Karyotype analyses rapidly identified loss of chromosome arms 1p and 19q as the most common genetic abnormality in oligodendrogliomas. Digital karyotyping identified OTX2 in medulloblastomas, and further studies revealed its frequent overexpression in anaplastic medulloblastomas. Recently, genome-wide sequencing identified three key pathways as mutated in the majority of glioblastomas, namely, the p53, retinoblastoma and receptor tyrosine kinase pathways. Further analysis may prove key to identifying likely therapeutic targets.

Key Concepts:

  • The most common primary malignant brain tumour of adults is glioblastoma, a grade IV astrocytoma with an average survival of approximately 1 year following diagnosis.
  • Recent genome-wide expression analyses have identified distinct expression patterns in glioblastoma patients which predict survival and may eventually be used to target therapies.
  • Three key pathways altered in the majority of astrocytomas include the receptor tyrosine kinase, p53 and retinoblastoma signalling pathways.
  • Epidermal growth factor receptor (EGFR) is overexpressed in the majority of glioblastomas and is frequently mutated to a constitutively active variant, EGFRvIII.
  • Mutations in IDH1 or IDH2 are the most common abnormality in both oligodendrogliomas and progressive astrocytomas, occurring in 60–90% of tumours.
  • The most characteristic chromosomal abnormality in oligodendrogliomas is complete allelic losses of chromosome 1p and 19q.
  • Gene expression microarray data has made possible the classification of medulloblastomas into subgroups based on expression of Sonic hedgehog pathway, Wnt pathway, neuronal differentiation or photoreceptor gene expression patterns.
  • The most common specific chromosomal abnormality in medulloblastomas is loss of 17p, which is often associated with gain of 17q.

Keywords: primary brain tumours; molecular techniques; inherited cancer syndromes

Figure 1. Proposed progression of gliomas. IDH1/2 mutations appear to be early genetic events in the development of oligodendrogliomas and progression astrocytomas, but not in primary GBMs. *Clinically, 5% of GBMs are progressive GBMs, whereas 30% of all GBMs exhibit mutations in TP53.
Figure 2. Receptor tyrosine kinase pathways in glioblastoma.
Figure 3. TP53 and Rb1 pathways in glioblastoma.
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Related Sub-Topics:

Neurobiology of Disease | Specific Genetic Disorders | Mutational Mechanisms of Genetic Disease | Cancer Genetics
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Article Title: Brain Tumours
 
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López, Giselle Y, Cummings, Thomas J, Bigner, Darell D, and McLendon, Roger E(Mar 2011) Brain Tumours. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006111.pub2]