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Title: Circulating nucleic acids as biomarkers of breast cancer
Author: Rghebi, Basma
ISNI:       0000 0004 6058 7886
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2017
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Background: Breast cancer is the commonest cancer and the second cause of cancer death among women. Two circulating biomarkers microRNAs (miRNAs) and circulating cell-free tumour DNA (cf-DNA) are currently under active investigation as a liquid biopsy for their utility in screening and management of breast cancer. Aims: The aim was to profile circulating miRNAs in plasma of breast cancer and compare to healthy controls to determine whether there were any miRNAs that differentially expressed in cancer. A second aim was to compare different methods to detect PIK3CA and TP53 mutations in breast cancer tissues DNA and cf-DNA. Methods: The expression level of 384 miRNAs in pooled plasma of breast cancer was compared to healthy controls using TaqMan microRNA array, followed by validation of specific miRNAs in single cancer and control plasma, using qPCR. Multiple different methods (qPCR, HRMC, ddPCR and Sanger sequencing) were compared for detection of PIK3CA or TP53 mutations in breast cancer tissue and matched plasma (cf-DNA). Results: 49 miRNAs (12.8%) showed significant expression change between pooled breast cancer plasma and controls. 11 of these were upregulated (P<0.05) in individual cancer plasma but there was wide variation in expression in controls. Overall, the ddPCR technology had higher sensitivity in detecting PIK3CA (0.1%) or TP53 (0.01%) mutations in cell line and breast cancer tissue than that achieved with other methods and overall 18 of 26 samples had a mutation in one or other gene. Conclusions: There was expression difference of a number of miRNAs in plasma of breast cancer compared to healthy controls, which needs further validation in other cohorts. The ddPCR was able to detect PIK3CA or TP53 mutations in breast cancer tissues with higher sensitivity than the other methods tested.
Supervisor: Shaw, Jacqueline Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available