Mutations in BRCA-1 and BRCA-2 predispose women to both breast and ovarian cancer. Cytogenetic analysis of epithelial ovarian cancers that are not familial often reveals complex karyotypic abnormalities, including structural lesions on chromosomes 1 and 11 and loss of heterozygosity for loci on chromosomes 3q, 6q, 11q, 13q, and 17. C-myc, H-ras, K-ras, and HER2/neu are often mutated or overexpressed. Unlike in colon cancer, a stepwise pathway to ovarian carcinoma is not apparent. Ovarian cancers may also occur in the setting of Lynch syndrome, inherited nonpolyposis colorectal cancer, due to mutations in the genes that repair DNA mismatches. The subset of women with endometrioid histology often have a mutation in ARID1A, a DNA repair complex component.
Section 6. Hematology and Oncology