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  • Review Article
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The Molecular and Genetic Basis of Neurological Tumours

Nature Reviews Cancer volume 2, pages 616–626 (2002)Cite this article

Key Points

  • Tumours of neuroectodermal origin (neurological tumours) include all neoplasms of the central nervous system (CNS) and peripheral nervous system (PNS). The classification of neurological tumours is based on their predominant cell type(s) as they relate to normal cell types that are present in the CNS and PNS.

  • Glial cells retain proliferative properties throughout life. So, most neurological tumours are of glial-lineage origin. In the CNS, gliomas include astrocytomas, oligodendrogliomas and oligoastrocytomas. In the PNS, neurofibromas and schwannomas are common tumours.

  • Genetic pathways that are involved in the initiation and progression of astrocytomas have been identified. In secondary glioblastoma multiforme (GBM), loss of p53 and activation of the growth-factor–receptor-tyrosine-kinase signalling pathway initiates tumour formation, whereas disruption of the retinoblastoma (RB) pathway contributes to the progression of tumour development.

  • Similar genetic pathways are disrupted in primary GBM, although through different mechanisms. The rapid growth nature of the primary GBM indicates that this type of malignancy might arise from the transformation of adult neural stem cells, which either are present in the brain or can be de-differentiated from astrocytes in response to oncogenic mutations.

  • Dermal neurofibromas are thought to be derived from a component of mature Schwann cells, whereas plexiform neurofibromas are believed to arise from an embryonic Schwann-cell lineage. Most malignant peripheral-nerve-sheath tumours are derived from neurofibromas — particularly plexiform neurofibromas.

  • Disruption of neurofibromatosis type 1 (NF1) in the Schwann-cell lineage initiates neurofibroma formation. In the setting of plexiform neurofibroma, the heterozygous state of tumour environment is important for tumour formation. The disruption of the p53 pathway is involved in the malignant progression of neurofibroma.

Abstract

There are no effective therapies for many tumours of the nervous system. This is, in part, a consequence of their location within relatively inaccessible tissues. It is also likely, however, that the unique characteristics of the cells that give rise to these tumours create a set of conditions that facilitate tumour development. Here, we consider recent advances in molecular genetics, the development of mouse models and developmental neurobiology as they relate to tumours of neuroectodermal origin. It is likely that these advances will provide insight into underlying mechanisms and provide a rational framework for the development of effective interventions.

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Figure 1: Developmental scheme of neuroectodermal (neurons and glia) cells and the classification of neurological tumours.
Figure 2: Genetic pathways involved in the development of primary and secondary astrocytoma.
Figure 3: Signalling pathway mediated by growth-factor–RTK.
Figure 4: A model for the development of primary GBM.
Figure 5: Development of Schwann cells and neurofibromas.

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Acknowledgements

The authors thank D. Burns, S. Kernie and L. Klesse for critically reading the manuscript. They also thank the members of the Parada lab for helpful discussions. L.F.P. is supported by NINDS (National Institute of Neurological Disorders and Stroke) and DOD (Department of Defence) grants. Y.Z. is a recipient of a Young Investigator Award from the NNFF (National Neurofibromatosis Foundation).

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Authors and Affiliations

  1. Center for Developmental Biology and Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, 75390-9133, Texas, USA

    Yuan Zhu & Luis F. Parada

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  1. Yuan Zhu
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Correspondence to Luis F. Parada.

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DATABASES

Cancer.gov

astrocytoma

brain tumours

ependymoma

GenBank

SV40 T antigen

LocusLink

Akt

AKT

CDC42

CDK2

Cdk4

CDK4

CDK6

CDKN2A

D-type cyclins

cyclin D1

E-type cyclins

E2F1

Egf

Egfr

EGFR

FGF2

Gfap

GFAP

GRB2

Ink4a

INK4B

INK4C

INK4D

KIP1

KIP2

MAPK

MDM2

MEK

nestin

Nf1

NF1

NRG1

p107

p120GAP

p130

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Pdgfa

PDGFA

Pdgfb

PDGFB

Pdgfr

PDGFR

PI3K

Pten

PTEN

RAC

RAF

Ras

RAS

RB

SHC

SOS

Trp53

WAF1

OMIM

Li–Fraumeni syndrome

neurofibromatosis type 1

Glossary

NEURAL-CREST CELLS

Cells that originate in the dorsal lip of the neural tube that undergo epithelial-to-mesenchymal transition and migrate outwards to give rise to all cells of the peripheral, autonomic and enteric nervous systems. These cells also give rise to melanocytes and neuroendocrine cells.

SCHWANNOMA

A neural-crest-derived tumour that has morphological and molecular features of Schwann cells. These tumours are clonal in origin.

PERIPHERAL-NERVE SHEATH

A strong flexible cable that is composed of collagen fibres and a cellular tube (perineurum) that ensheaths, insulates and protects peripheral-nerve bundles.

SCHWANN CELL

A glial-cell component of the peripheral nervous system that is derived from the neural crest and composed of myelinating and non-myelinating cells.

PERINEURAL CELL

A mesenchyme-derived cell that is recruited by forming peripheral nerves to undergo mesenchymal-to-epithelial transformation. These cells form the perineurum and secrete matrix that forms the perineural sheath.

PHEOCHROMOCYTOMA

A neuroendocrine tumour that is formed in neural-crest-derived adrenal chromaffin cells.

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Zhu, Y., Parada, L. The Molecular and Genetic Basis of Neurological Tumours. Nat Rev Cancer 2, 616–626 (2002). https://doi.org/10.1038/nrc866

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