Document Detail

Molecular genetic analysis of p53 intratumoral heterogeneity in human astrocytic brain tumors.
MedLine Citation:
PMID:  17917588     Owner:  NLM     Status:  MEDLINE    
We investigated genetic heterogeneity of astrocytic gliomas using p53 gene mutations as a marker. Different parts of morphologically heterogeneous astrocytic gliomas were microdissected, and direct DNA sequencing of p53 gene exons 5 through 8 was performed. Thirty-five glioma samples and tumor-adjacent normal-appearing brain tissue from 11 patients were analyzed. Sixteen different p53 gene mutations were found in 7 patients. We found that some tumors were devoid of p53 gene mutations, whereas other tumors carried 1 or often several (up to 3) different mutations. The mutations were present in grade II, III, and IV astrocytic glioma areas. Both severe functionally dead mutants and mutants with remaining transcriptional activity could be observed in the same tumor. We observed that morphologically different parts of a glioma could carry different or similar mutations in the p53 gene and could be either associated or not associated with the locus of heterozygosity at the mutant site. Coexistence of p53 gene mutations and the locus of heterozygosity was common, at least in astrocytomas grade III and in glioblastomas, and also occurred in astrocytoma grade II areas. These results support the notion that intratumoral heterogeneity in brain tumors originates from different molecular defects. Our results are of importance for a further understanding of the molecular mechanisms behind failure to treat glioma patients.
Zhi-Ping Ren; Tommie Olofsson; Mingqi Qu; Göran Hesselager; Thierry Soussi; Hannu Kalimo; Anja Smits; Monica Nistér
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuropathology and experimental neurology     Volume:  66     ISSN:  0022-3069     ISO Abbreviation:  J. Neuropathol. Exp. Neurol.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-05     Completed Date:  2007-11-06     Revised Date:  2008-01-16    
Medline Journal Info:
Nlm Unique ID:  2985192R     Medline TA:  J Neuropathol Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  944-54     Citation Subset:  IM    
Department of Genetics and Pathology, Uppsala University, University Hospital, Uppsala, Sweden.
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MeSH Terms
Astrocytoma / genetics*,  pathology
Brain Neoplasms / genetics*,  pathology
DNA Primers
DNA, Neoplasm / genetics
Gene Frequency
Genes, p53 / genetics*,  physiology
Loss of Heterozygosity
Middle Aged
Mutation / genetics,  physiology
Reverse Transcriptase Polymerase Chain Reaction
Reg. No./Substance:
0/DNA Primers; 0/DNA, Neoplasm

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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