Loss of heterozygosity at chromosomes 3, 6, 8, 11, 16, and 17 in ovarian cancer: correlation to clinicopathological variables

Tumor specimens from 78 epithelial ovarian cancer patients were examined fo r loss of heterozygosity (LOH) at II microsatellite markers at chromosomes 3p14.2, 6q27, 8p12, 11p15.5, 11q23.1-q24, 16q24.3, and 17p13.1, to evaluate the involvement, possible clustering, and prognostic significance of these lesions in the progression of the disease. The LOH analysis was performed on polymerase chain reaction (PCR)-amplified DNA from sections of paraffin- embedded tumor and normal tissue pairs. In addition to primary tumors, spec imens of metastatic tissues were studied from 19 patients. In the combined results from primary and metastatic tumors, LOH frequencies varied between 31% (6q27) and 69% (17p13.1). Only LOH at chromosomal regions 3p14.2 (D3S13 00), 11p15.5 (D11S1318), 11q23.3-q24 (D11S1340 and D11S912), 16q24.3 (D16S4 76 and D16S3028) and 17p13.1 (D17S938) was associated with an adverse disea se course. Our results indicate that LOH at 17p13.1 occurs independently fr om the other chromosomal sites studied, and is an early event in ovarian tu morigenesis. The LOH at 16q24.3, 11q23.3/q24, and 11p15.5 seems to occur la ter. The LOH at 11p15.5 and 11q23.3 was associated with reduced cancer-spec ific survival time; therefore, the studied markers could be located close t o genes with influence on patient survival. Of the studied chromosomal regi ons, the most important tumor suppressor genes involved in the evolution of ovarian cancer appear to be located on chromosomes 11, 16, and 17. The gen etic heterogeneity observed in primary and metastatic specimens demonstrate s that there are multiple pathways involved in the progression of ovarian c ancer. (C) 2000 Elsevier Science Inc. All rights reserved.