Molecular genetic changes in human epithelial ovarian malignancies

The frequent finding of loss of heterozygosity (LOH) for a specific chromosomal marker in tumor DNA compared to normal DNA suggests the presence of a closely linked tumor-suppressor gene. Using Southern blot analysis, 34 primary ovarian epithelial tumors were examined for the presence of tumor-specific allelic losses, using six probes for chromosomes 6q, 11p, 13q, 16q, and 17p. A high incidence of LOH was observed on 11p, 13q, and 17p. LOH for 17p was present in 3 of 4 (75%) informative benign ovarian tumors, 1 of 5 (20%) borderline tumors, and 16 of 24 (67%) invasive ovarian cancers. Allelic loss with the H-ras1 probe on 11p was present in 10 of 19 (53%) invasive tumors but was not identified in 6 benign or borderline tumors. LOH on 13q was present in 18 of 31 (58%) informative cases including 8 of 10 (80%) Stage 1 tumors. This preliminary study suggests that loss of tumor-suppressor genes on chromosomes 13q and 17p may be early events in ovarian tumorigenesis and that changes on chromosome 11p are later events.