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Current and Emerging Applications of Droplet Digital PCR in Oncology

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Abstract

The clinical management of cancer has evolved in recent years towards more personalized strategies that require a comprehensive knowledge of the complex molecular features involved in tumor growth and evolution, and the development of drug resistance mechanisms leading to disease progression. Droplet digital PCR (ddPCR) has become one of the most accurate and reliable tools for the examination of genetic alterations in a wide variety of cancers because of its high sensitivity and specificity. ddPCR is currently being applied for absolute allele quantification, rare mutation detection, analysis of copy number variations, DNA methylation, and gene rearrangements in different kinds of clinical samples. This methodology has proven useful for the evaluation of archival tumor tissues, where poor DNA quality and limited sample availability are major obstacles for standard methods, providing less subjective and more automated quantitative results. However, most applications of ddPCR in cancer are focused on liquid biopsies (including cell-free DNA as well as circulating tumor cells) because these represent non-invasive alternatives to tissue biopsies that can more accurately reflect intratumoral heterogeneity and track the dynamic changes in tumor burden that occur in response to treatment at different times during follow-up. A broad spectrum of molecular markers have been interrogated in blood using ddPCR for diagnostic, predictive, and monitoring purposes in various malignancies. Emerging alternative approaches using other body fluids such as cerebrospinal fluid and urine are also currently being developed. This article aims to give a complete overview of ddPCR applications for molecular screening in oncology.

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Acknowledgements

The authors gratefully acknowledge the editors and reviewers for their valuable comments and suggestions, which contributed to improve the quality of this article.

Author Contributions

SO-L wrote the manuscript. MG-A and DG-O reviewed the manuscript. All authors agreed on the final version.

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Authors and Affiliations

  1. New Therapies Laboratory, Foundation Health Research Institute-Fundación Jiménez Díaz University Hospital (FIIS-FJD), Avda. Reyes Católicos, 2, 28040, Madrid, Spain

    Susana Olmedillas-López, Mariano García-Arranz & Damián García-Olmo

  2. Department of Surgery, School of Medicine, Universidad Autónoma de Madrid (UAM), 28029, Madrid, Spain

    Mariano García-Arranz & Damián García-Olmo

  3. Department of Surgery, Fundación Jiménez Díaz University Hospital (FJD), 28040, Madrid, Spain

    Damián García-Olmo

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  1. Susana Olmedillas-López
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  2. Mariano García-Arranz
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  3. Damián García-Olmo
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Correspondence to Susana Olmedillas-López.

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Susana Olmedillas-López is a post-doctoral researcher at the Foundation Health Research Institute-Fundación Jiménez Díaz University Hospital (FIIS-FJD), Madrid, from the RETIC Program of ISCIII-FEDER (RD12/0019/0035). This work is part of a grant from “Fondo de Investigaciones Sanitarias-FEDER”, Ministry of Health, Spain (FIS; PI13/01924).

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Susana Olmedillas-López, Mariano García-Arranz, and Damián García-Olmo declare that they have no conflicts of interest.

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Olmedillas-López, S., García-Arranz, M. & García-Olmo, D. Current and Emerging Applications of Droplet Digital PCR in Oncology. Mol Diagn Ther 21, 493–510 (2017). https://doi.org/10.1007/s40291-017-0278-8

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