CORRELATION OF TP53 MUTATIONS AND P53 EXPRESSION IN OVARIAN-TUMORS

To characterize the involvement of the TP53 tumor suppressor gene in o varian cancer, mutation analysis of exons 2-11 of TP53 and immunodetec tion of its protein product, p53, were done in 48 ovarian tumors. Norm ally, p53 is not immunodetectable. Missense TP53 mutations have been r eported to result in p53 accumulation and detection, but mutations gen erating premature stop codons have not. Mutations were identified in 1 9 of 41 malignant tumors but not in 5 benign tumors and 2 tumors of lo w malignant potential. Fifteen of the 19 tumors with mutations also st ained 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 tu mors with frameshifts also had a wild-type TP53 allele and displayed n ormal 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 i s 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 nucleotid e substitutions with 6 transitions and 7 transversions. The ratio of t ransversions to transitions (1.2) was different from literature report s (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. (C) Elsevier Science Inc., 1998