title: p53 and PTEN gene mutations in gemistocytic astrocytomas.
abstract: The gemistocytic astrocytoma is a histological variant of diffuse astrocytomas and is characterised by the presence of large, GFAP-expressing neoplastic astrocytes (gemistocytes) and a tendency towards rapid progression to glioblastoma. In this study, we analyzed 28 gemistocytic astrocytomas (mean fraction of gemistocytes, 35.0+/-9.9%) for mutations in the p53 and PTEN (MMAC1) tumour suppressor genes. Single strand conformation polymorphism (SSCP), followed by direct DNA sequencing of p53 exons 5-8, revealed a mutation in 23 of 28 (82%) cases. Regional analysis of four tumours revealed identical p53 mutations in gemistocytic and fibrillary tumour areas. In contrast, none of 15 gemistocytic astrocytomas (WHO Grade II) and only two of 11 (18%) anaplastic gemistocytic astrocytomas (WHO Grade III) contained a PTEN mutation. Of these, one was a 1 bp deletion in codon 345 and the other a 1 bp insertion in intron 4. Differential PCR did not reveal homozygous PTEN deletion in any of the tumours analysed. These results indicate that p53 mutations are a genetic hallmark of gemistocytic astrocytomas, whilst PTEN mutations are absent in low-grade and rare in anaplastic gemistocytic astrocytomas.
authors.affiliation: Unit of Molecular Pathology, International Agency for Research on Cancer, Lyon, France.
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: A
authors.initials: A
authors.lastname: Peraud
authors.forename: C
authors.initials: C
authors.lastname: Gratas
authors.forename: S
authors.initials: S
authors.lastname: Wakai
authors.forename: P
authors.initials: P
authors.lastname: Kleihues
authors.forename: H
authors.initials: H
authors.lastname: Ohgaki
mesh_terms: D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D016158:Genes, p53; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human