Although ovarian cancer is the most lethal tumor of the female genital tract, molecular mechanism of tumor development have not yet fully been understood. The loss of heterozygosity on chromosome 3, 6, 11 and 17 has been reported to occur
frequently in
ovarian cancer, suggesting the involvement of tumor suppressor gene inactivation in the development of ovarian cancer. It became clear that p53 tumor suppressor gene could be a prime target for genetic alteration in sporadic human malignancies
such
as
lung, colon, breast and ovary. Activating mutations seem to concentrate in a portion of the gene spanning codons 132-281, corresponding to exons 5-8, and do not seem to conform to a particular pattern, since they range from nucleotide
substitution
to
deletions of variable length.
The objectives of this study were to define the sites, nature and incidence of the mutations of p53 tumor supressor gene in epithelial ovarian cancer and to determine the focality(unifocal or multifocal origin) of epithelial ovarian cancer and
the
stage(early or late event) of the genetic alterations by comparing these mutations in primary tumors with those in metastases.
Using polymerase chain reactio with primers for exon 5, 6, 7 and 8 followed by direct DNA sequencing technique, we analysed 61 fresh frozen ovarian cancer samples(primary tumor and metastases) from 23 patients with epithelial ovarian cancer who
were
surgically treated in Asan Medical Center.
Twelve point mutations were indentified from five(21.7%) of the patients tested. Mutations were shown in exons 5 and 8, but no preferential pattern of nucleotide substitution could be observed.
In the cases showing two or more sites with mutations(case 7, 10, 16) the natures of nucleotide substitution in DNA from different sites within the same patient were identical. This suggests that ovarian carcinomas have unifocal origin. And it
was
noticeable that mutations were observed in all primary lesions(ovaries), but in only a few sites of metastatic lesions, suggesting that p53 mutations may occur late during ovarian cancer evolution.
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