Virchows Archiv

, Volume 427, Issue 2, pp 113–118

Genetic alterations associated with the evolution and progression of astrocytic brain tumours

  • H. Ohgaki
  • P. Kleihues
  • B. Schäuble
  • A. zur Hausen
  • K. von Ammon
Review Article

DOI: 10.1007/BF00196514

Cite this article as:
Ohgaki, H., Kleihues, P., Schäuble, B. et al. Vichows Archiv A Pathol Anat (1995) 427: 113. doi:10.1007/BF00196514

Abstract

Diffusely infiltrating low-grade astrocytomas (WHO grade II) have an intrinsic tendency for progression to anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV). This change is due to the sequential acquisition of genetic alterations, several of which have recently been identified. In low-grade astrocytomas, p53 mutations with or without loss of heterozygosity on chromosome 17p are the principal detectable change. Anaplastic astrocytomas contain p53 mutations at an overall incidence of 34% and, in addition, loss of heterozygosity on chromosome 19q and frequent homozygous deletion of the p16 tumor suppressor (MTS-1) gene. The most malignant astrocytic neoplasms, the glioblastoma, further shows loss of chromosome 10 and amplification of the epidermal growth factor receptor (EGF-R) gene at overall incidences of 66% and 34%, respectively. The type and distribution of p53 mutations in astrocytic brain tumours are not suggestive of specific environmental carcinogens operative in their aetiology. Analysis of 91 families with p53 germline mutations reported to date show that tumours of the nervous system account to 12% of all neoplasms. Of a total of 57 brain tumours reported, 30 were classified histologically and of these, 73% were of astrocytic origin. The observation that somatic p53 mutations in sporadic brain tumours are largely restricted to those of astrocytic origin and that astrocytomas also prevail among CNS neoplasms associated with p53 germline mutation strongly suggests, that p53 mutations are capable of initiating neoplastic transformation in astrocytes of the human nervous system.

Key words

Astrocytoma Oncogene Tumour suppressor gene 

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • H. Ohgaki
    • 1
  • P. Kleihues
    • 1
    • 2
  • B. Schäuble
    • 2
  • A. zur Hausen
    • 2
  • K. von Ammon
    • 3
  1. 1.International Agency for Research on Cancer (IARC)LyonFrance
  2. 2.Institute of Neuropathology, Department of PathologyUniversity HospitalZurichSwitzerland
  3. 3.Department of NeurosurgeryUniversity HospitalZurichSwitzerland

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