p53 expression, mutation, and allelic deletion in ovarian cancer.
The aim of this investigation was to study the prevalence of p53 gene mutations and allelic deletions in ovarian cancer and the relationship between these events and p53 expression. Genomic p53 was amplified by the polymerase chain reaction (PCR) from paraffin-embedded sections of tumour and non-tumour tissue. Exons 5-9 were screened for mutation using non-isotopic single-strand conformation polymorphism (SSCP) analysis. Allelic deletions at a sequence polymorphism in exon 4 were studied for loss of heterozygosity (LOH) by restriction analysis and by SSCP. p53 expression was detected by immunohistochemistry with the p53 antibodies CM1 and Do7. Of 44 cases, ten (23 per cent), including a mucinous tumour of low malignant potential, showed mutations. There was a statistically significant correlation between p53 mutation and expression (P < 0.01) but seven cases showed discordance. Of 18 informative cases, eight (44 per cent) demonstrated LOH. Mutations were identified in three of the informative cases, two of which also had LOH. The remaining case showed mutations in two amplicons. p53 dysfunction, as indicated by mutation, deletion, or increased expression, is common in ovarian cancer. There is an association between these molecular events but the exact mechanisms of p53 inactivation remain to be elucidated.
McManus
D T
DT
Department of Pathology, Royal Victoria Hospital, Belfast, U.K.
Yap
E P
EP
Maxwell
P
P
Russell
S E
SE
Toner
P G
PG
McGee
J O
JO
D000483:Alleles; D001483:Base Sequence; D002872:Chromosome Deletion; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D015995:Prevalence; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D016159:Tumor Suppressor Protein p53