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Investigation of quantitative and qualitative MtDNA alteration in breast cancer

Fan, Xiucheng. Investigation of quantitative and qualitative MtDNA alteration in breast cancer. 2009, PhD Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_8811

Abstract

Mitochondrial DNA (mtDNA) alterations including copy number variations and sequence variations are suspected to be associated with carcinogenesis. We established a multiplex quantitative real-time PCR to examine the quantities of mtDNA and nuclear DNA (nDNA) for analysing relative mtDNA content in blood and tissue samples of patients with breast cancer. We also developed a novel matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) based MicroARRAY multiplex assay to identify mtDNA sequence variants at 22 nucleotide positions (np) in a single reaction.
For the quantitative analysis, mtDNA content was significant decreased in cancerous breast tissues (51 cases) compared with the paired normal breast tissues (p = 0.000). The down-regulation of mtDNA was observed in 82% of the cancerous samples. The similar down-regulation has been also found in whole blood and plasma samples from patients with breast cancer. Using the MALDI-TOF MS, we analysed the 22 mtDNA mutations related to breast cancer in the 51 paired breast tissues (cancerous and normal). 154 mtDNA mutations were found in total, 49.35% in cancerous tissues and in 50.65% in paired normal samples. Forty one tissue samples contain more than 2 mutations each. All these sequence variants were distributed at 5 np in a hotspot region around the displacement loop (D-loop). We investigated the relationship between the quantitative and qualitative mtDNA alterations in breast tissues, as well as the correlation between the alterations of mtDNA and some clinical/pathological parameters, such as patient age, tumour type, tumour size, lymph node involvement, extent of metastasis, stage, histological grading, and ER, PR, and HER-2/neu receptors in breast cancer. No associations were found between the quantitative and qualitative changes, as well as between the mtDNA changes and clinical/pathological parameters.
Our data suggest that mtDNA alterations are indeed involved in breast cancer. Investigating mtDNA alterations in cancer might be helpful for developing biomarkers in the management of cancer patients. The methods used in this study for the investigation can be introduced as simple, accurate and cost-efficient tools.
Advisors:Hall, Michael N.
Committee Members:Lindberg Gasser, Raija L.P. and Zhong, Xiao Yan
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
Item Type:Thesis
Thesis no:8811
Bibsysno:Link to catalogue
Number of Pages:171
Language:English
Identification Number:
Last Modified:30 Jun 2016 10:41
Deposited On:08 Jan 2010 08:58

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