Mutations of the p53 tumor suppressor gene in neoplasms of the human nervous system.
A variety of neoplasms of the human nervous system were analyzed for the presence of mutations in the p53 tumor suppressor gene. DNA was extracted from frozen or formalin-fixed, paraffin-embedded material. Single-strand conformation polymorphism (SSCP) analysis for exons 5-8 was followed by direct DNA sequencing. Mutations leading to an amino acid change were found in three of 11 (27%) low-grade (World Health Organization (WHO) Grade II) astrocytomas. They were located in codon 183 (TCA-->TGA) of exon 5, codon 237 (ATG-->ATA) of exon 7, and codon 273 (CGT-->CAT) of exon 8. In one of these cases, the sequence indicated loss of the wild-type allele. Of 12 juvenile pilocytic astrocytomas (WHO Grade I), none contained a p53 mutation, suggesting a different molecular basis for this childhood neoplasm. Except for a mutation in one of seven (14%) meningeal hemangiopericytomas (codon 238; TGT-->TTT, Cys-->Phe), no mutations were observed in exons 5-8 of the p53 gene in any of the following tumors of the nervous system and its coverings: 13 schwannomas, 12 central neurocytomas, 22 meningiomas, 10 choroid plexus papillomas and carcinomas, and 30 neuroblastomas of the sympathetic nervous system. These and published data support the view that p53 mutations are frequently involved both in low-grade and progressive (anaplastic) astrocytomas, including glioblastomas multiforme. Oligodendrogliomas, medulloblastomas, meningiomas, and hemangiopericytomas rarely (< 15%) show p53 mutations in exons 5-8, whereas none of the remaining nervous system neoplasms revealed evidence of an involvement of the p53 gene in their development.
Department of Pathology, University Hospital, Zürch, Switzerland.
H
H
Ohgaki
R H
RH
Eibl
M
M
Schwab
M B
MB
Reichel
L
L
Mariani
M
M
Gehring
I
I
Petersen
T
T
Höll
O D
OD
Wiestler
P
P
Kleihues
D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003062:Codon / Q000235:genetics; D004273:DNA, Neoplasm / Q000737:chemistry / Q000302:isolation & purification; D004277:DNA, Single-Stranded / Q000737:chemistry; D005091:Exons / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006393:Hemangiopericytoma / Q000235:genetics*; D006801:Humans; D008297:Male; D008579:Meningioma / Q000235:genetics; D008875:Middle Aged; D008968:Molecular Conformation; D009423:Nervous System Neoplasms / Q000235:genetics*; D009442:Neurilemmoma / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics; D018306:Neurocytoma / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D003062:Codon; D004273:DNA, Neoplasm; D004277:DNA, Single-Stranded