Recurrent cytogenetic aberrations and loss of constitutional heterozygosity in ovarian carcinomas

Abstract

Cancer is regarded as the result of the accumulation of multiple genetic changes leading to either the activation of oncogenes and increased expression of mitogenic pathways or the inactivation of tumor suppressor genes. It was our interest to investigate malignant ovarian tumors with cytogenetic and molecular techniques to evaluate their consistent genetic alterations. Cytogenetic analysis was performed on 30 short-term cultured ovarian carcinomas. Fifteen tumors revealed clonal cytogenetic abnormalities, 10 of which had very complex karyotypes. The most consistent finding was a 19p+ marker chromosome which was present in half of the cytogenetically abnormal tumors with complex chromosome aberrations. Four tumors showed structural rearrangements resulting in loss of 11p13-pter material. Parallel DNA extracts from 18 tumor samples and corresponding normal white blood cells were analyzed by Southern blotting using 4 polymorphic probes spanning the region 11p15.1 to 11p15.5 and one polymorphic probe mapped to 19p13. Regarding the 11p probes, reduction to homozygosity in the tumor DNA was found in 9 of 17 informative cases. Loss of 19p alleles was found in 5 of 13 informative tumors. Our findings suggest that tumor suppressor genes located on the short arms of chromosomes 11 and 19 are involved in the development of human ovarian cancer.