Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Korting, J.
Circulating tumor DNA in sarcoma patients: liquid biopsy as a non-invasive method for treatment monitoring
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2022. pp. 50
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Kashofer Karl
- Altmetrics:
- Abstract:
- This diploma thesis deals with the applications of liquid biopsy in sarcomas. Sarcomas are rare, malignant tumors with poor prognosis, affecting mainly young patients. They arise from mesenchymal tissue and can be broadly classified into soft tissue and bone tumors. Many sarcomas have specific translocations. Translocations occur when chromosomes break into pieces and the fragmented parts are reattached to other chromosomes. In contrast to other tumor entities, overall survival has not improved in recent years, which has to do with the great heterogeneity and rarity of sarcomas. Diagnosis is made by needle biopsy and monitoring of therapy is mainly via radiological diagnosis. This is because repeated biopsies are too much of a burden for the mostly young patients. Liquid biopsy, on the other hand, is a minimally invasive method. The aim of this work is to explore whether the detection of circulating tumor DNA by digital-droplet PCR is suitable to monitor the therapy of sarcoma patients. The analyzed cohort included 18 study participants with different entities of sarcomas. Whole-genome sequencing was used to analyze the genetic changes and determine the breakpoints, which are mostly located in the introns. The breakpoints of the translocations in the different tumor entities could be determined in 15 of 18 samples. This provided the necessary information to generate the required probes for ddPCR. Thus, the tumor-specific structurally altered DNA molecules in plasma were searched for by using individually designed ddPCR approaches. Overall, ctDNA was detected in 26% of the samples, including all Ewing Sarcomas and one Synovial Sarcoma. The results show that our approach of using LB as a means to monitor the treatment of sarcoma patients is a promising option. In one case, the ddPCR results were considered in conjunction with the clinical course. Here, the ddPCR results were found to be congruent with the radiological and clinical examinations, respectively. At one point in time, ctDNA could already be detected when PET-CT was still unremarkable. Many other studies also highlight the potential of liquid biopsies for therapy monitoring, detection of residual tumor cells, and early detection of relapse. For the potential to be fully exploited, the analytical validity and clinical utility need to be investigated in large, randomized clinical trials.