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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

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Circulating tumor DNA and their added value in molecular oncology

Math P.G. Leers
  • Corresponding author
  • Department of Clinical Chemistry and Hematology, Zuyderland Medical Center Sittard-Geleen, Dr. H. Van der Hoffplein 1, P.O. Box 5500, 6130 MB Sittard, The Netherlands
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Published Online: 2019-09-06 | DOI: https://doi.org/10.1515/cclm-2019-0436


New methods for molecular diagnosis are now available in oncology thanks to the discovery of circulating tumor DNA molecules in the plasma of cancer patients. By utilizing blood samples, rather than traditional tissue sampling, clinical practice is on the verge of new discoveries from the analysis of cell-free DNA (cfDNA). The method, known as a “liquid biopsy”, consists of analyzing therapeutic targets and drug-resistant conferring gene mutations in circulating tumor cells (CTC) and cell-free circulating tumor DNA (ctDNA). These are subsequently released from primary tumors and metastatic deposits into the peripheral blood. The advantages of the method can be observed in the diagnosis, but also in the choice of treatment for solid tumors (e.g. non-small cell lung carcinomas [NSCLC]). In order to interpret the results, an understanding of the biological characteristics of circulating tumor DNA is required. Currently there is no consensus as to how a liquid biopsy should be conducted. In this review, we will assess the pros of ctDNA as analytes in peripheral blood samples and its impact on clinical applications in solid tumors and hematological malignancies. We will also address practical issues facing clinical implementation, such as pre-analytical factors. Moreover, we will emphasize the open questions that remain when considering the current state of personalized medicine and targeted therapy.

Keywords: cell-free DNA; circulating tumor DNA; liquid biopsy; somatic mutations; tumor heterogeneity


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About the article

Corresponding author: Math P.G. Leers, PhD, Department of Clinical Chemistry and Hematology, Zuyderland Medical Center Sittard-Geleen, Dr. H. Van der Hoffplein 1, P.O. Box 5500, 6130 MB Sittard, The Netherlands, Phone: +31-88-4597503

Received: 2019-04-26

Accepted: 2019-08-06

Published Online: 2019-09-06

Author contributions: MPGL wrote the manuscript. The author has accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), 20190436, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2019-0436.

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