Intracranial germ cell tumors: detection of p53 gene mutations by single-strand conformation polymorphism analysis.
Using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis, p53 gene mutation was examined in 12 intracranial germ cell tumors (5 yolk sac carcinomas and 7 germinomas), many of which were derived from young patients in the first to the second decade. A total of 10 mutations were detected in 4 of the 12 cases and, in 3 of them, the mutations were multiple or tandem. Among the 10 mutations, 7 were missense, 1 was splicing and 2 were silent. The 7 missense mutations were located at previously proposed hot spot codons or in their vicinity or, when outside the hot spots, at a codon encoding an amino acid conserved in most vertebrates. These findings suggested that all 7 missense mutations may actually give rise to functional alteration of the p53 protein. The splicing mutation was considered to be a germ-line mutation, though its biological effect was equivocal, since the neoplastic tissue contained an additional mutation. The pattern of the mutations was predominancy of G:C-A:T transition with frequent involvement of the CpG site. These mutations were more frequently detected in yolk sac carcinomas (60%; 3/5 cases) than in germinomas (14%; 1/7 cases), suggesting that the contribution of the p53 mutation to carcinogenesis differed with the histological type of the intracranial germ cell tumor.
Feng
X
X
Department of Neuropathology, Niigata University.
Zhang
S
S
Ichikawa
T
T
Koga
H
H
Washiyama
K
K
Motoyama
T
T
Kumanishi
T
T
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics*; D002648:Child; D018240:Endodermal Sinus Tumor / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D018237:Germinoma / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational