Brain Tumours


Brain tumour genetics allow for improved classification and development of therapeutic options for 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, tuberous sclerosis and Turcot syndrome. Advances in genetic profiling, including karyotypic analyses, genome‐wide sequencing, epigenetic studies and gene expression studies, have greatly improved the understanding of the genetic basis for these tumours. Genome‐wide sequencing identified three key pathways as mutated in the majority of primary glioblastomas, namely, the p53, retinoblastoma and receptor tyrosine kinase pathways. These studies have also identified characteristic genetic alterations in many tumours, such as IDH1/2 mutations in oligodendrogliomas and progressive astrocytomas, TERT promoter mutations in primary glioblastomas and oligodendrogliomas and BAF47 loss in atypical teratoid/rhabdoid tumours. Further analysis may prove key to identifying likely the 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.
  • The specific genetic alterations present in brain tumours are critical to prognosis and treatment decisions; new diagnostic criteria for brain tumours now integrate molecular classification with the previous histologic classification.
  • Genome‐wide expression analyses have identified distinct expression patterns in primary glioblastoma patients which predict survival and may eventually be used to target therapies.
  • Three key pathways altered in the majority of primary glioblastomas include the receptor tyrosine kinase, p53 and retinoblastoma signalling pathways.
  • Mutations in IDH1 or IDH2 are the most common abnormality in both oligodendrogliomas and progressive astrocytomas, making these tumours genetically distinct from primary glioblastoma.
  • The most characteristic chromosomal abnormality in oligodendrogliomas is complete allelic losses of chromosomes 1p and 19q.
  • Gene expression microarray data has made possible the classification of medulloblastomas into four subgroups: Sonic hedgehog pathway subgroup, Wnt pathway subgroup, group 3 and group 4.
  • Many paediatric brain tumours are characterised by alterations in genes involved in histone/chromatin modifications.

Keywords: primary brain tumours; molecular techniques; inherited cancer syndromes; glioma; medulloblastoma; mutations; amplifications

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 glioblastomas.
Figure 2. Receptor tyrosine kinase pathway.
Figure 3. TP53 and retinoblastoma pathways.


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Further Reading

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López, Giselle Y, Cummings, Thomas J, Bigner, Darell D, and McLendon, Roger E(Nov 2016) Brain Tumours. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0006111.pub3]