Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Auer, M.
High-resolution molecular characterization of circulating cell-free DNA and circulating tumor cells of patients with metastatic breast cancer.
[ Diplomarbeit/Master Thesis (FH) ] Fachhochschule FH Campus Wien; 2012. pp.121.
- Autor*innen der Med Uni Graz:
- Auer Martina
- Betreuer*innen:
- Geigl Jochen Bernd
- Altmetrics:
- Abstract:
- With the increasing number of available predictive biomarkers, clinical management of cancer is becoming more and more reliant on the accurate serial monitoring of tumor genotypes. Recent advances in the understanding of the molecular mechanisms of cancer have highlighted the need for personalized medicine approaches not only in terms of prognosis but also for diagnostic strategies. Extensive work has resulted in the identification of biological indicators that have been implemented in cancer clinical practice at several levels. These biomarkers are extremely useful and their discovery will be further accelerated by the recent advances in cancer genomics. Over the past years, the identification of somatic mutations and/or genetic polymorphisms has facilitated detection of disease and has helped to stratify patients according to response treatment. In this study, the identification of such biomarkers from circulating cell-free (cf) DNA and circulating tumor cells (CTC) of patients with metastatic breast cancer was performed. We addressed whether complex tumor genomes may be inferred non-invasively from the peripheral blood of patients with cancer. 46 patients with metastatic breast cancer, 5 patients in complete remission and 8 healthy controls were enrolled in the evaluation. Cf-DNA concentration was determined and followed by a qualitative and quantitative analysis for subsequent high-resolution whole-genome characterization. Regarding CTCs an enumeration and, in some cases isolation and further high-molecular characterization was done. A subset of patients with biphasic size distribution of cf-DNA fragments was identified to be associated with an increase of circulating tumor cells and elevated concentrations of cf-DNA as well as mutated cf-DNA fragments. In these cases it was possible to establish a method to follow tumor-specific copy number alterations directly from cf-DNA using array-CGH technology. The techniques used in this study allow a serial monitoring of tumor genomes with a simple blood test. The results yield novel insights regarding basic research questions, such as processes underlying metastases and tumor evolution, while also covering clinical aspects such as biomarker status and individualized therapies. However, there is the focus on the true complexity of tumor genome status out of peripheral blood and not only on a single marker.