Gliomagenesis: genetic alterations and mouse models

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Abstract
Gliomas are primary tumours that arise from glial cells in the brain and spinal cord. The most malignant gliomas — glioblastoma multiforme (GBM) — are nearly always fatal. Treatment strategies for this disease have remained unchanged for many years and most are based on a limited understanding of the biology of the disease. Chromosomal instability and the deletion and amplification of certain genes are a hallmark of the more severe clinical grades of human glioma. The cells of malignant gliomas share certain characteristics with undifferentiated glial progenitor cells. Mutations found in GBMs frequently activate the signalling pathways that control the differentiation and proliferation of these progenitors or disrupt cell-cycle arrest pathways. Recapitulating the genetic alterations found in human gliomas in mouse models gives rise to tumours that histologically resemble human gliomas. These mouse models have given clues as to the molecular origins of gliomas, and should contribute to the design and testing of new rational therapies.