Abstract
Digital PCR techniques are ideally suited for accurately quantifying trace amounts of target DNA sequences, such as tumor-derived mutant DNA that is present in the blood circulation of patients with cancer. Here, we describe an approach marrying low-coverage whole-genome sequencing of tumor tissues, to enumerate chromosomal rearrangement breakpoints, together with droplet digital PCR (ddPCR)-based personalized rearrangement assays to cost-effectively monitor circulating tumor DNA levels at multiple time-points during the clinical course. The method is generally applicable to essentially any cancer patient, as all cancers harbor unstable genomes, and may have uses for measuring minimal residual disease, response to therapy, and early detection of metastasis.
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Acknowledgments
We thank members of the Translational Oncogenomics Unit, Division of Oncology and Pathology for assistance, and in particular to Christof Winter and Robert Rigo for bioinformatics work. This work was supported by the Swedish Cancer Society, Swedish Research Council, Swedish Foundation for Strategic Research, Knut and Alice Wallenberg Foundation, VINNOVA, and Governmental Funding of Clinical Research within National Health Service, Swedish Breast Cancer Group, Crafoord Foundation, Lund University Medical Faculty, Gunnar Nilsson Cancer Foundation, Skåne University Hospital Foundation, BioCARE Research Program, King Gustav Vth Jubilee Foundation, Krapperup Foundation, and the Mrs. Berta Kamprad Foundation.
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Chen, Y., George, A.M., Olsson, E., Saal, L.H. (2018). Identification and Use of Personalized Genomic Markers for Monitoring Circulating Tumor DNA. In: Karlin-Neumann, G., Bizouarn, F. (eds) Digital PCR. Methods in Molecular Biology, vol 1768. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7778-9_17
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DOI: https://doi.org/10.1007/978-1-4939-7778-9_17
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