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Title: Molecular analysis of sporadic breast cancer in younger women
Author: Johnson, Suzanne Michelle
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2001
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This thesis presents molecular genetic evidence to support the hypothesis that sporadic breast carcinomas occurring in this younger age group are biologically different. 31 cases of infiltrating ductal carcinoma occurring in women aged 35 years were analysed for loss of heterozygosity and microsatellite instability at 10 polymorphic microsatellite markers in three key chromosomal intervals: 17p 13 (p53), 17q 11-21 (BRACA1 ) and 13q 12-13 (BRCA2). An elevated incidence of LOH was detected at BRCA1(65%) and BRCA2 (74%) when compared to a control group of matched postmenopausal cases (aged 55-72 years) of 35% and 40% LOH respectively (x2 = 5.22, 1 d.f. P < 0.025, x2 = 12.6, 1d.f. P<0.01). MSI was rare. 17/28 cases aged 35 years showed reduced expression of BRCA1 at the mRNA level by RT-PCR, and LOH at BRCA1 was detected in 13 of these (x2 = 5.22 (1d.f.) 0.025. 0.01). In addition, BRCA1 protein expression was reduced or absent in the tumours in comparison to a control group of 31 normal breast samples taken from reduction mammoplasties. 10/31 cases aged 35 years were positive for p53 expression using immunohistochemistry and SSCP analysis of exons 5-8 revealed altered migration in 9/10 cases. Sequencing confirmed the presence of missense mutations in the DNA binding domain in two of the tumours. In summary, these data demonstrate a high frequency of genetic alterations supporting a role for BRCA1, BRCA2 and p53 in the development of this particular group of sporadic breast carcinomas in young women.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available