TP53 polymorphisms and haplotypes in breast, cervical and ovarian cancer
TP53 polymorphisms and haplotypes in breast, cervical and ovarian cancer
There is evidence that carcinoma develops through an accumulation of mutations in the cellular DNA. Unregulated cellular growth that occurs in cancer is normally prevented by inhibitory proteins that are coded for by tumour suppressor genes (TSGs). The TSG TP53 has a fundamental role in maintaining genomic integrity by inducing growth arrest in DNA damaged cells and if the damage is too extreme inducing programmed cell death. Inactivation of this system is therefore a key event in carcinogenesis and not surprisingly TP53 is the most frequently mutated gene in human cancers. In cervical cancers, inactivation of TP53 more commonly occurs at an epigenetic level by interaction with HPV-16/18 oncoprotein E6. Germline polymorphisms in TP53 may alter the activity and susceptibility of the p53 protein to degradation. The role of three different p53 polymorphisms (codon 72 pro/arg, a 16bp duplication in intron 3 and an MSP 1 RFLP in intron 6) was investigated in the development of breast and ovarian carcinoma and human papillomavirus (HPV) associated cervical cancer to assess whether based on extended haplotypic analysis, women at increased risk could be identified for additional screening.
DNA was extracted from cervical smear samples for 265 women with CIN, archival paraffin histological specimens for 38 women with cervical cancer and blood leucocytes for 266 women with ovarian cancer, 369 women with breast cancer and 254 controls residents in the Wessex region. TP53 polymorphism determination by PCR and restriction analysis was performed to calculate the relative allelic frequencies in the study group. For each locus the alleles are designated 1 for proline and 2 for arginine at codon 72: 1 for deletion and 2 for insertion in intron 3: 1 for Msp restriction site absent and 2 for restriction site present in intron 6.
University of Southampton
Gornall, Robert James
5356499c-3061-47b8-90d4-a7c6190531a0
1999
Gornall, Robert James
5356499c-3061-47b8-90d4-a7c6190531a0
Gornall, Robert James
(1999)
TP53 polymorphisms and haplotypes in breast, cervical and ovarian cancer.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
There is evidence that carcinoma develops through an accumulation of mutations in the cellular DNA. Unregulated cellular growth that occurs in cancer is normally prevented by inhibitory proteins that are coded for by tumour suppressor genes (TSGs). The TSG TP53 has a fundamental role in maintaining genomic integrity by inducing growth arrest in DNA damaged cells and if the damage is too extreme inducing programmed cell death. Inactivation of this system is therefore a key event in carcinogenesis and not surprisingly TP53 is the most frequently mutated gene in human cancers. In cervical cancers, inactivation of TP53 more commonly occurs at an epigenetic level by interaction with HPV-16/18 oncoprotein E6. Germline polymorphisms in TP53 may alter the activity and susceptibility of the p53 protein to degradation. The role of three different p53 polymorphisms (codon 72 pro/arg, a 16bp duplication in intron 3 and an MSP 1 RFLP in intron 6) was investigated in the development of breast and ovarian carcinoma and human papillomavirus (HPV) associated cervical cancer to assess whether based on extended haplotypic analysis, women at increased risk could be identified for additional screening.
DNA was extracted from cervical smear samples for 265 women with CIN, archival paraffin histological specimens for 38 women with cervical cancer and blood leucocytes for 266 women with ovarian cancer, 369 women with breast cancer and 254 controls residents in the Wessex region. TP53 polymorphism determination by PCR and restriction analysis was performed to calculate the relative allelic frequencies in the study group. For each locus the alleles are designated 1 for proline and 2 for arginine at codon 72: 1 for deletion and 2 for insertion in intron 3: 1 for Msp restriction site absent and 2 for restriction site present in intron 6.
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Published date: 1999
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Local EPrints ID: 464058
URI: http://eprints.soton.ac.uk/id/eprint/464058
PURE UUID: 54c44b23-632e-453f-bb2c-ca8b6852bdac
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Date deposited: 04 Jul 2022 21:01
Last modified: 23 Jul 2022 02:05
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Author:
Robert James Gornall
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