Mitochondrial DNA as a Breast Cancer Biomarker

In this thesis, we extended the exploration on the value of cell-free DNA (cfDNA) and mitochondrial DNA (mtDNA) alterations as a cancer biomarker. First, by quantification of the number of mtDNA molecules per cell in primary tumours we explored the association with established clinicopathological biomarkers (Chapter 2 and 3), and investigated the prognostic (Chapter 2) and predictive (Chapter 3) potential of mtDNA content in patients with breast cancer. The exploration of mtDNA as a putative biomarker in breast cancer was further extended by exploring somatic variants and expression of the mitochondrial transcriptome in primary breast cancer samples, and assessed for their association with established clinicopathological markers (Chapter 4). Next, to investigate mtDNA in blood, we set up a pipeline to analyse the genetic make-up of cfDNA in retrospective – and thus limiting amounts of – breast cancer patient material (Chapter 5). In addition, we established a sensitive and specific approach to profile mtDNA (Chapter 6). The knowledge acquired from the efforts described in Chapter 5 and 6 were applied in a cohort of retrospectively selected breast and colon cancer patients to explore the feasibility of tumour-specific mtDNA variant detection in cfDNA as a cancer biomarker (Chapter 7).

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