Genetic alterations associated with the evolution and progression of astrocytic brain tumours
- 1 September 1995
- journal article
- review article
- Published by Springer Science and Business Media LLC in Virchows Archiv
- Vol. 427 (2), 113-118
- https://doi.org/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.Keywords
This publication has 39 references indexed in Scilit:
- Homozygous deletions of the multiple tumor suppressor gene 1 in the progression of human astrocytomas.1995
- CDKN2 (p16/MTS1) gene deletion or CDK4 amplification occurs in the majority of glioblastomas.1994
- Amplification of multiple genes from chromosomal region 12q13-14 in human malignant gliomas: preliminary mapping of the amplicons shows preferential involvement of CDK4, SAS, and MDM2.1994
- The 1993 Walter Hubert Lecture: the role of the p53 tumour-suppressor gene in tumorigenesisBritish Journal of Cancer, 1994
- The New WHO Classification of Brain TumoursBrain Pathology, 1993
- Deletions on the long arm of chromosome 17 in pilocytic astrocytomaActa Neuropathologica, 1993
- Association of epidermal growth factor receptor gene amplification with loss of chromosome 10 in human glioblastoma multiformeJournal of Neurosurgery, 1992
- p53 mutation and loss of heterozygosity on chromosomes 17 and 10 during human astrocytoma progression.1992
- Amplification of Epidermal Growth Factor Receptor Gene in Gliomas: Histopathology and PrognosisJournal of Neuropathology and Experimental Neurology, 1992
- Grading of astrocytomas: A simple and reproducible methodCancer, 1988