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Molecular genetic analysis of chromosome 22q in ovarian cancer

Molecular genetic analysis of chromosome 22q in ovarian cancer
Molecular genetic analysis of chromosome 22q in ovarian cancer

The loss of chromosome 22q in ovarian cancer has been well documented, however conflicting results have been reported. The initial aim of this study, was to establish the overall frequency of LOH on chromosome 22q using the technique of loss of heterozygosity (LOH). By using a large number of microsatellite markers it has been confirmed that LOH on 22q is a very frequent event in ovarian carcinomas.

The data presented here has enabled refinement of candidate tumour suppressor gene (TSG) loci, the first of which lies in an approximately 500Kb region at 22q13.1. A second putative TSG loci was localised to a 6cM region at the telomeric end of 22q. By analysing LOH with respect to the individual histological sub-types, grades and stages of the ovarian tumours available it was demonstrated that loss of genes on chromosome 22q is of greater relevance in serous and endometrioid tumours and may occur at an early stage of tumour development in these sub-types.

Once the candidate regions had been firmly established a physical map using bacteriophage P1-derived artificial chromosomes (PACs) was constructed of the smaller 500Kb region in order to begin the process of identifying the TSG harboured in this region. The most promising gene identified was the human P48 gene which is involved in the formation of the mature progesterone receptor complex. The procedure of single stranded conformational polymorphism (SSCP) analysis was utilised to establish if the P48 gene is mutated in ovarian cancer, however this proved not to be the case. The cytochrome P450, CYP2D6 lay on the most proximal boundary of this 500Kb region and as it exists in several forms leading to differential efficiencies of metabolism, a genotype analysis was carried out on the ovarian cancer population, this study failed to identify a role for this gene in ovarian tumourigenesis.

University of Southampton
Bryan, Emma Jane
bc84741e-5ec2-4f70-bde4-56ec4b5e4396
Bryan, Emma Jane
bc84741e-5ec2-4f70-bde4-56ec4b5e4396

Bryan, Emma Jane (1998) Molecular genetic analysis of chromosome 22q in ovarian cancer. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

The loss of chromosome 22q in ovarian cancer has been well documented, however conflicting results have been reported. The initial aim of this study, was to establish the overall frequency of LOH on chromosome 22q using the technique of loss of heterozygosity (LOH). By using a large number of microsatellite markers it has been confirmed that LOH on 22q is a very frequent event in ovarian carcinomas.

The data presented here has enabled refinement of candidate tumour suppressor gene (TSG) loci, the first of which lies in an approximately 500Kb region at 22q13.1. A second putative TSG loci was localised to a 6cM region at the telomeric end of 22q. By analysing LOH with respect to the individual histological sub-types, grades and stages of the ovarian tumours available it was demonstrated that loss of genes on chromosome 22q is of greater relevance in serous and endometrioid tumours and may occur at an early stage of tumour development in these sub-types.

Once the candidate regions had been firmly established a physical map using bacteriophage P1-derived artificial chromosomes (PACs) was constructed of the smaller 500Kb region in order to begin the process of identifying the TSG harboured in this region. The most promising gene identified was the human P48 gene which is involved in the formation of the mature progesterone receptor complex. The procedure of single stranded conformational polymorphism (SSCP) analysis was utilised to establish if the P48 gene is mutated in ovarian cancer, however this proved not to be the case. The cytochrome P450, CYP2D6 lay on the most proximal boundary of this 500Kb region and as it exists in several forms leading to differential efficiencies of metabolism, a genotype analysis was carried out on the ovarian cancer population, this study failed to identify a role for this gene in ovarian tumourigenesis.

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Published date: 1998

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Local EPrints ID: 463388
URI: http://eprints.soton.ac.uk/id/eprint/463388
PURE UUID: 8fc56210-7cb2-45fe-a3e3-b3b0a653a5e5

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Date deposited: 04 Jul 2022 20:51
Last modified: 23 Jul 2022 01:09

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Author: Emma Jane Bryan

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