Genomic Assessment of Ovarian Cancer

This chapter reviews the genomic assessment of ovarian cancer. The normal human ovary is lined by a cuboidal epithelium. These cells remain quiescent for most of their lifespan, proliferating only to repair the ovarian surface after ovulation. Epidemiologic evidence demonstrates a clear correlation between the frequency of ovulation and the incidence of epithelial ovarian cancer. As a result, particular attention in the search for precursors to ovarian cancer has focused on small inclusion clefts that persist after repair of the ovarian surface. The molecular environment influencing these clefts is unique-the epithelia lining these clefts express specific cell adhesion molecules, including cadherins, not normally observed in other areas of the ovarian surface epithelium. Linkage analysis of familial breast and ovarian cancers provided insights into the molecular basis of ovarian cancer. Improved means to detect and/or eradicate the lesions may prove fruitful for preventing ovarian cancer. Research efforts, designed to improve the early detection of ovarian cancer or optimize its clinical management at later stages, are likely to be more successful based on the understanding of molecular events responsible for this disease. These efforts identify two genes, BRCA1 and BRCA2, each clearly associated with an increased incidence of ovarian cancer. About 60% of familial ovarian cancers are associated with mutations at the BRCA1 locus. The BRCA2 gene plays a role in DNA repair by homologous recombination. About 35% of hereditary ovarian cancers may be attributed to BRCA2 mutations. © 2010