Ovarian carcinoma is the most frequent cause of death from gynecological malignancies in the Western world. It ranks fifth overall as a cause of death from cancer in women, with over 12,000 deaths per year, and an estimated 20,000 new cases will be diagnosed in 1991. Most cases are diagnosed at an advanced stage due to a paucity of clinical symptoms until late in disease progression. Prognosis is poor, with an overall five-year survival of about 30%. Recently, tumor-specific allele losses of chromosomes 6, 11, and 17 have been reported, as well as abnormalities on chromosomes 1 and 3. Amplification of the erbB2 oncogene on chromosome 17q occurs in 30% of cases, and other oncogenes, including K-ras and myc, have been discovered to be amplified in a few ovarian tumors and cell lines. The loss of tumor-suppressor genes at certain chromosomal loci may also be important in the pathogenesis of ovarian carcinoma, as it has been shown to be in other human tumors. In order to directly investigate the molecular genetic aberrations leading to altered gene expression in ovarian neoplasia compared to normal tissue, cDNA libraries from matched tumor/normal tissues were constructed. Tumor minus normal and normal minus tumor libraries were constructed to enrich for tumor-specific and normal-specific cDNAs, respectively, with the aim of identifying genes critical in the process of carcinogenesis (tumor promoter genes), or for maintaining the normal state (tumor suppressor genes). In addition, ovarian carcinoma samples are analyzed for the presence of altered known tumor-suppressor genes, such as p53 and the retinoblastoma gene, Rb. Direct sequencing of PCR-amplified segments may show sequence abnormalities contributing to the inactivation or malfunction of these genes.
