title: Alterations in oncogenes, tumor suppressor genes, and growth factors associated with epithelial ovarian cancers.
abstract: More than 90% of epithelial ovarian cancers are clonal neoplasms that arise from the progeny of a single cell (1-3). Comparison of primary and metastatic sites from the same patient has detected similar patterns of loss of heterozygosity (LOH) on different chromosomes, inactivation of the same X chromosome, and identical mutations in the p53 gene in primary and secondary tumors. Given the clonality of most ovarian cancers, multiple genetic alterations must occur in the progeny of a single cell to permit progression from a normal epithelial phenotype to that of a malignant cell capable of uncontrolled proliferation, invasion, and metastasis. Approximately 10% of ovarian cancers are familial and have been associated with germ-line mutations in BRCA1, BRCA2, mismatch repair genes, or p53 (detailed in Subheading 2.2.). Somatic mutations have been found in sporadic ovarian cancers that activate oncogenes or that result in loss of tumor suppressor gene function. Different ovarian cancers can also exhibit aberrant autocrine and/or paracrine growth regulation with alteration in the expression of growth factors and their receptors. No single abnormality has been detected in all ovarian cancers and most of the alterations are observed in cancers that arise at other sites. Certain changes in oncogenes, tumor suppressor genes, growth factors, and their receptors occur in a significant fraction of epithelial ovarian cancers, whereas others are uncommon. Consequently, progress has been made in defining the spectrum and profile of genetic and epigenetic changes that occur during transformation of the ovarian epithelium. A better understanding of the genotypic and phenotypic alterations that are associated with different epithelial ovarian cancers may impact on more effective management of the disease through chemoprevention, early detection, precise prognostication, treatment directed toward molecular targets, and individualization of therapy.
authors.affiliation: Department of Obstetrics and Gynecology, Duke University Medical Center, NC.
authors.forename: R C
authors.initials: RC
authors.lastname: Bast
authors.forename: G B
authors.initials: GB
authors.lastname: Mills