p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma

Loss of genetic material on the short arm of chromosome 17 is observed in approximately 40% of human astrocytomas (WHO grades II and III) and in approximately 30% of cases of glioblastoma multiforme (WHO grade IV). Previous studies of glioblastoma multiforme have shown that the p53 gene, located on...

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Bibliographic Details
Published in:	Cancer research (Chicago, Ill.) Vol. 52; no. 10; pp. 2987 - 2990
Main Authors:	VON DEIMLING, A, EIBL, R. H, OHGAKI, H, LOUIS, D. N, VON AMMON, K, PETERSEB, I, KLEIHUES, P, CHUNG, R. Y, WIESTLER, O. D, SEIZINGER, B. R
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 15-05-1992
Subjects:	Alleles Astrocytoma - genetics Astrocytoma - pathology Base Sequence Biological and medical sciences Blotting, Southern Chromosome Deletion Chromosomes, Human, Pair 17 - physiology DNA, Single-Stranded - genetics Exons - genetics Genes, p53 - genetics Heterozygote Humans Medical sciences Molecular Sequence Data Mutation Neurology Nucleic Acid Conformation Polymorphism, Genetic Polymorphism, Restriction Fragment Length Tumors of the nervous system. Phacomatoses Chromosomal aberration Histological grading Human Intracranial Nervous system diseases Pathogenesis Exploration Malignant tumor Glioblastoma multiforme Restriction fragment length polymorphism Abnormal chromosome Mutation Molecular biology Astrocytoma Abnormal E17 chromosome Tumor suppressor gene
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Summary:	Loss of genetic material on the short arm of chromosome 17 is observed in approximately 40% of human astrocytomas (WHO grades II and III) and in approximately 30% of cases of glioblastoma multiforme (WHO grade IV). Previous studies of glioblastoma multiforme have shown that the p53 gene, located on the short arm of chromosome 17, is frequently mutated in these glioblastomas. To explore whether lower-grade astrocytomas are also associated with corresponding mutations of the p53 gene, we have investigated a series of 22 human astrocytomas of WHO grades II and III both for loss of heterozygosity on chromosome 17p and for p53 mutations. Mutations in the conserved regions of the p53 gene were identified by single strand conformation polymorphism analysis of exons 5, 6, 7, and 8 and were verified by direct DNA sequencing of the polymerase chain reaction products. p53 mutations were observed in 3 of 8 grade II astrocytomas and 4 of 14 grade II astrocytomas. In all 22 tumors, allelic loss of the short arm of chromosome 17 was investigated by restriction fragment length polymorphism analysis. One-half of the grade II astrocytomas (4 of 8) and grade III astrocytomas (7 of 14) exhibited allelic loss on chromosome 17p. Mutations in the p53 gene were exclusively observed in tumors with allelic loss on 17p. Our results show that p53 mutations are not restricted to glioblastoma multiforme and may be important in the tumorigenesis of lower-grade astrocytomas and that p53 mutations in lower-grade astrocytomas are associated with loss of chromosome 17p. These findings are consistent with a recessive mechanism of action of p53 in WHO grade II and III astrocytoma tumorigenesis.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0008-5472 1538-7445