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The molecular genetics of human brain tumors

Venter, Deon Jacobus; (1990) The molecular genetics of human brain tumors. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

A series of 13 benign and 27 malignant human gliomas was analysed to define the fundamental molecular genetic abnormalities underlying glioma development. Southern analysis of restriction fragment length polymorphisms was used to assess loss of chromosomal material in tumour DNA, an event compatible with dysfunction of putative tumour suppressor genes. Chromosomes 10, 13q and 17p were selected for study on the basis of previously described cytogenetic abnormalities in gliomas. In addition, the integrity of the retinoblastoma gene on chromosome 13q, as well as the putative tumour suppressor gene p53 on chromosome 17p, was assessed. Tumour DNA was also examined for amplification of the epidermal growth factor receptor (EGFR), N-mvc and c-erbB-2 oncogenes. The results indicated that specific molecular lesions were associated with increasing grades of malignancy. Thus, loss of genetic material on chromosome 17 was present in both benign and malignant gliomas, whereas loss of loci on chromosomes 10 and 13 was seen only in malignant gliomas. A structural abnormality of the retinoblastoma gene coding region was detected in one glioblastoma. Amplification of the EGFR oncogene was present in 5 malignant gliomas. In contrast to other tumours studied, only glioblastomas contained more than one molecular abnormality in the same tumour. The relevance of these findings to our understanding of the molecular mechanisms underlying tumour development and to their effect on improving the accuracy of tumour diagnosis are discussed. In a further set of experiments, the NIH3T3 transfection assay was used to reveal the presence of activated oncogenes in the genome of human cell lines thought to be derived from gliomas. One cell line contained an activated oncogene. This oncogene was identified, by oligonucleotide hybridisation to polymerase chain reaction-amplified DNA, as an N-ras gene with a codon 61 mutation. However, it was demonstrated by DNA fingerprinting that the supposed human glioma cell line had been previously contaminated with cells of rhabdomyosarcoma origin.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The molecular genetics of human brain tumors
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10111303
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