HIGH PREVALENCE OF CODON 213(ARG-]STOP) MUTATIONS OF THE TP53 GENE INHUMAN OVARIAN-CANCER IN THE SOUTHWESTERN PART OF THE NETHERLANDS

As in many human malignancies, TP53 mutations ave the most common gene tic alterations in malignant human ovarian tumours, An approach often used in the determination of TP53 status is immunohistochemical staini ng of the protein. Non-missense mutations, especially those of the nul l type, causing premature termination codons and resulting in truncate d proteins, may often not be detectable by immunohistochemistry. There fore, current estimates of TP53 alterations in ovarian cancer may be i naccurate. By using polymerase chain reaction-single strand conformati on polymorphism analysis and sequencing techniques, we have found a hi gh prevalence of TP53 non-missense mutations in exons 5-8 in ovarian t umour specimens from patients from the southwestern part of The Nether lands. Twenty-nine of 64 tumours showed mutations, of which 10 were no n-missense mutations. The majority (9 of 10) of these non-missense mut ations, including 7 nonsense mutations and 2 frameshift deletions, wer e null type mutations and could not be detected by immunohistochemical staining. Five of the 7 nonsense mutations were mutations at codon 21 3 (Arg-Stop), The nature of the high prevalence of this nonsense mutat ion in our series of ovarian carcinomas remains unknown. In addition t o the 9 null type mutations, a splice junction mutation was encountere d. In conclusion, we have observed a high prevalence (13%) of ovarian tumours with null type mutations in exons 5-8 that did not result in i mmunostaining. Our data suggest that, especially in ovarian cancer, im munological assessment of TP53 is not an adequate tool to study TP53 a lteration, A frequent nonsense mutation at codon 213 in 5 (8%) of 64 t umour specimens represents an important finding. (C) 1998 Wiley-Liss, Inc.