Correlation of TP53 mutations and p53 expression in ovarian tumors.
To characterize the involvement of the TP53 tumor suppressor gene in ovarian cancer, mutation analysis of exons 2-11 of TP53 and immunodetection of its protein product, p53, were done in 48 ovarian tumors. Normally, p53 is not immunodetectable. Missense TP53 mutations have been reported to result in p53 accumulation and detection, but mutations generating premature stop codons have not. Mutations were identified in 19 of 41 malignant tumors but not in 5 benign tumors and 2 tumors of low malignant potential. Fifteen of the 19 tumors with mutations also stained positively by immunohistochemistry or Western blot or both. They included 11 missense mutations, 1 in-frame duplication (474ins6), and 3 frameshift mutations generating premature stop codons. The three tumors with frameshifts also had a wild-type TP53 allele and displayed normal size but not truncated p53 by Western blot. This indicates that these tumors express wild-type p53. The significance of TP53 mutations in the development of the three tumors is questionable unless there is a mechanism for inactivating wild-type p53. Nine of the 19 mutations found here, including the 3 frameshifts, were previously not reported in ovarian cancer. Thirteen of the 19 mutations were single nucleotide substitutions with 6 transitions and 7 transversions. The ratio of transversions to transitions (1.2) was different from literature reports (0.5) (P < 0.01). Thus, the spectrum of TP53 mutations in our study differed from other ovarian tumor reports. This difference may be due to population-based differences in the molecular epidemiology of TP53 mutations.
DiCioccio
R A
RA
Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Werness
B A
BA
Peng
R
R
Allen
H J
HJ
Piver
M S
MS
D015153:Blotting, Western; D018388:Codon, Terminator / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology
D018388:Codon, Terminator; D016159:Tumor Suppressor Protein p53