p53 mutation, allele loss on chromosome 17p, and DNA content in ovarian carcinoma.
The aim of this investigation was to explore the relationships between p53 mutation, DNA aneuploidy, 17p deletions, and clinical stage in ovarian cancer. Nuclear suspensions were obtained by tissue disaggregation, stained with propidium iodide, and analysed on a Coulter EPICS Elite flow cytometer. DNA cell cycle analysis was performed using Multicycle software (Phoenix Flow Systems). DNA extracted from paraffin-embedded archival carcinomas/non-tumour tissue was used as template for PCR amplification of the microsatellite dinucleotide repeat polymorphism D17S513, a locus telomeric to p53 on 17p13.1. Allele loss at D17S513 was detected in 64.5 per cent of carcinomas (20 of 31 informative cases). DNA aneuploidy was detected in 20 of 54 (37 per cent) carcinomas. Eight of ten cases previously shown to harbour p53 mutations showed aneuploid DNA content. Although ten other DNA aneuploid cases had shown no p53 mutations, the results show a statistically significant association between p53 mutation and DNA aneuploidy (P < 0.01). Furthermore, the mean DNA index of the DNA aneuploid cases was significantly higher in p53 mutant cases compared with those showing no p53 mutation (P = 0.02). There was also a significant association between p53 mutations and stage, between ploidy and stage, and between allelic deletions at D17S513 or p53 and stage, but not between these allelic deletions and ploidy. p53 mutations appear to be associated with DNA aneuploidy in ovarian cancer independently of 17p deletions. p53 mutations, DNA aneuploidy, and 17p deletions are associated with late stage.
McManus
D T
DT
Pathogenesis and Molecular Medicine Research Divisions, Queen's University of Belfast, U.K.
Murphy
M
M
Arthur
K
K
Hamilton
P W
PW
Russell
S E
SE
Toner
P G
PG
D000483:Alleles; D001483:Base Sequence; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D016158:Genes, p53 / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011003:Ploidies; D016133:Polymerase Chain Reaction
D004273:DNA, Neoplasm