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Tumor-specific genetic aberrations in cell-free DNA of gastroesophageal cancer patients

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Abstract

The applicability of liquid biopsies is studied intensively in all types of cancer and analysis of circulating tumor DNA (ctDNA) has recently been implemented clinically for mutation detection in lung cancer. ctDNA may provide information about tumor quantity and mutations present in the tumor, and as such have many potential applications in diagnosis and treatment of cancer. It has been suggested that ctDNA analysis may overcome the issue of intra-tumor heterogeneity faced by tissue biopsies and serve as an additional diagnostic tool. Furthermore, liquid biopsies are potentially helpful for monitoring of treatment response as well as detection of minimal residual disease and relapse. Gastroesophageal cancers (GEC) have high mortality rates and the majority of patients present with advanced stage at diagnosis or succumb due to disease recurrence even after radical resection of the primary tumor. Biomarkers that can help optimize treatment strategy are thus highly desirable. The present study is a review of published data on ctDNA in GEC patients. We identified 25 studies in which tumor-specific genetic aberrations were investigated in plasma or serum and discuss these in relation to the methods applied for ctDNA analysis. The methods used for ctDNA detection greatly influence the sensitivity of the analysis and, therefore, the potential clinical applications. We found that studies of ctDNA in GEC, although limited in number, are promising for several applications such as genetic profiling of tumors and monitoring of disease progression. However, more studies are needed to establish if and how this analysis can be clinically implemented.

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Acknowledgements

This work was supported by funding from Odense University Hospital (grants from Free Research Funds, “Overlægerådets forskningsfond”, and “Frontlinjepuljen”), University of Southern Denmark, and the Frimodt Heineke Foundation.

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Authors and Affiliations

  1. Department of Clinical Genetics, Odense University Hospital, J.B. Winsløws Vej 4, Odense, Denmark

    Kristina Magaard Koldby, Mads Thomassen & Torben A. Kruse

  2. Human Genetics, Department of Clinical Research, University of Southern Denmark, Sdr. Boulevard 29, Odense, Denmark

    Kristina Magaard Koldby, Mads Thomassen & Torben A. Kruse

  3. Department of Surgery, Odense University Hospital, J.B. Winsløws Vej 4, Odense, Denmark

    Michael Bau Mortensen

  4. Department of Pathology, Odense University Hospital, J.B. Winsløws Vej 15, Odense, Denmark

    Sönke Detlefsen

  5. Department of Oncology, Odense University Hospital, J.B. Winsløws Vej 4, Odense, Denmark

    Per Pfeiffer

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  1. Kristina Magaard Koldby
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Koldby, K.M., Mortensen, M.B., Detlefsen, S. et al. Tumor-specific genetic aberrations in cell-free DNA of gastroesophageal cancer patients. J Gastroenterol 54, 108–121 (2019). https://doi.org/10.1007/s00535-018-1508-5

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