Molecular genetic analysis of chromosome 7 and its role in human ovarian cancer

Abstract

Loss of heterozygosity (LOH) of chromosome 7q has been shown to occur frequently in many tumour types including that of the ovary, suggesting the presence of a tumour suppressor gene (TSG). This investigation used thirty-four microsatellite markers from across chromosome 7 to analyse LOH in a large bank of over 200 primary epithelial ovarian tumours. Several distinct regions of LOH were identified indicating that chromosome 7 may harbour more than one tumour suppressor gene associated with ovarian cancer. The data presented here suggests that chromosome 7 LOH is an early event in ovarian tumorigenesis, and potentially involved in the switch from benign or borderline disease to malignancy.

Three genes from the most commonly deleted regions at 7q22 and 7q31 were analysed for mutations. The proto-oncogene c-MET at 7q31, did not exhibit any mutations and does not appear to be the gene being targeted for deletion in this region. PAI-1, a member of the plasminogen/plasmin proteolytic pathway previously implicated in tumour growth and metastasis, did not appear to harbour any mutations within its coding region, strongly suggesting that it is not involved in the LOH observed at 7q22 in ovarian cancer. Another 7q22 candidate, CUTL1, a putative repressor of gene expression, revealed a polymorphism within a 'cut repeat' domain, and several silent, intronic, germline alterations. The lack of functional mutations implies that CUTL1 is not the 7q22 TSG candidate.

This study also demonstrates the ability to identify LOH and genetic mutations in DNA isolated from the blood plasma of ovarian cancer patients.

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