An investigation of tumour suppressor genes on chromosome 11 in ovarian cancer

Manolitsas, Thomas (1998) An investigation of tumour suppressor genes on chromosome 11 in ovarian cancer. University of Southampton, Doctoral Thesis.

Abstract

The aims of this study were to investigate two hypotheses; 1: that PROGINS (a common insertional polymorphism in the progesterone receptor gene) has an association with ovarian cancer, and that the progesterone receptor (PR) gene may be acting as a tumour suppressor gene (TSG) in ovarian cancer, and 2: that TSG101, a novel gene located on chromosome 11p15.1-15.2, is a TSG in ovarian cancer.

The incidence of the PROGINS allele was found to be virtually identical in a group of 230 ovarian cancer patients compared to a group of 220 non-cancer controls. The rate of loss of heterozygosity (LOH) amongst those patients heterozygous for the PROGINS allele was found to be 30%. However in each case the loss involved the PROGINS allele and not the wild type allele as predicted. It was concluded that it was unlikely that the PROGINS polymorphism was important in the development of ovarian cancer, but that another region on or near to the PR gene may be acting as a TSG.

Analysis of 97 cases of primary ovarian epithelial cancer showed an overall LOH rate of 45% for chromosome 11p. The LOH rate at any of the three markers tested specifically in the region of TSG101 was 8% for mucinous and 51% for non mucinous tumours. These results suggest the presence of a TSG in this region which is associated with the development of epithelial ovarian cancer but not those of mucinous histological subtype.

This study provides evidence in support of the hypothesis that TSG101 may be acting as a TSG in ovarian cancer, but does not support the hypothesis that PROGINS is associated with ovarian cancer or that the PR gene is a TSG in ovarian cancer.

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