Brain Tumours

Abstract

AbstractBrain 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 fluorescencein situhybridisation (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 identifiedOTX2in 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, thep53, retinoblastoma and receptortyrosine kinasepathways. 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.