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Article

Technical Evaluation of Commercial Mutation Analysis Platforms and Reference Materials for Liquid Biopsy Profiling

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Institute of Human Genetics, Diagnostic & Research Center for Molecular BioMedicine, Medical University of Graz, 8010 Graz, Austria
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Christian Doppler Laboratory for Liquid Biopsies for Early Detection of Cancer, Medical University of Graz, 8010 Graz, Austria
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Institute of Pathology, Diagnostic & Research Center for Molecular BioMedicine, Medical University of Graz, 8010 Graz, Austria
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University of Groningen, University Medical Center of Groningen, 9713 GZ Groningen, The Netherlands
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LGC SeraCare Life Sciences, Milford, MA 01757, USA
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Cancer Research UK MI, University of Manchester, Manchester SK10 4TG, UK
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Agena Bioscience GmbH, 22761 Hamburg, Germany
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Bayer AG, Biomarker Research, 42113 Wuppertal, Germany
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QIAGEN GmbH, 40724 Hilden, Germany
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University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
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Department of Cancer Genetics, Institute of Cancer Research, Oslo University Hospital, N-0310 Oslo, Norway
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(6), 1588; https://doi.org/10.3390/cancers12061588
Received: 30 March 2020 / Revised: 15 May 2020 / Accepted: 11 June 2020 / Published: 16 June 2020
(This article belongs to the Special Issue Liquid Biopsy: Latest Advances and Future Challenges)
Molecular profiling from liquid biopsy, in particular cell-free DNA (cfDNA), represents an attractive alternative to tissue biopsies for the detection of actionable targets and tumor monitoring. In addition to PCR-based assays, Next Generation Sequencing (NGS)-based cfDNA assays are now commercially available and are being increasingly adopted in clinical practice. However, the validity of these products as well as the clinical utility of cfDNA in the management of patients with cancer has yet to be proven. Within framework of the Innovative Medicines Initiative (IMI) program CANCER-ID we evaluated the use of commercially available reference materials designed for ctDNA testing and cfDNA derived from Diagnostic Leukaphereses (DLA) for inter- and intra-assay as well as intra- and inter-laboratory comparisons. In three experimental setups, a broad range of assays including ddPCR, MassARRAY and various NGS-based assays were tested. We demonstrate that both reference materials with predetermined VAFs and DLA samples are extremely useful for the performance assessment of mutation analysis platforms. Moreover, our data indicate a substantial variability of NGS assays with respect to sensitivity and specificity highlighting the importance of extensive validation of the test performance before offering these tests in clinical routine practice. View Full-Text
Keywords: ctDNA; circulating tumor DNA; cfDNA; cell-free DNA; molecular profiling; mutation analysis; reference material; diagnostic leukaphereses; assay validation; performance assessment ctDNA; circulating tumor DNA; cfDNA; cell-free DNA; molecular profiling; mutation analysis; reference material; diagnostic leukaphereses; assay validation; performance assessment
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MDPI and ACS Style

Weber, S.; Spiegl, B.; Perakis, S.O.; Ulz, C.M.; Abuja, P.M.; Kashofer, K.; van der Leest, P.; Azpurua, M.A.; Tamminga, M.; Brudzewsky, D.; Rothwell, D.G.; Mohan, S.; Sartori, A.; Lampignano, R.; Konigshofer, Y.; Sprenger-Haussels, M.; Wikman, H.; Bergheim, I.R.; Kloten, V.; Schuuring, E.; Speicher, M.R.; Heitzer, E. Technical Evaluation of Commercial Mutation Analysis Platforms and Reference Materials for Liquid Biopsy Profiling. Cancers 2020, 12, 1588. https://doi.org/10.3390/cancers12061588

AMA Style

Weber S, Spiegl B, Perakis SO, Ulz CM, Abuja PM, Kashofer K, van der Leest P, Azpurua MA, Tamminga M, Brudzewsky D, Rothwell DG, Mohan S, Sartori A, Lampignano R, Konigshofer Y, Sprenger-Haussels M, Wikman H, Bergheim IR, Kloten V, Schuuring E, Speicher MR, Heitzer E. Technical Evaluation of Commercial Mutation Analysis Platforms and Reference Materials for Liquid Biopsy Profiling. Cancers. 2020; 12(6):1588. https://doi.org/10.3390/cancers12061588

Chicago/Turabian Style

Weber, Sabrina, Benjamin Spiegl, Samantha O. Perakis, Christine M. Ulz, Peter M. Abuja, Karl Kashofer, Paul van der Leest, Maria A. Azpurua, Menno Tamminga, Dan Brudzewsky, Dominic G. Rothwell, Sumitra Mohan, Alexander Sartori, Rita Lampignano, Yves Konigshofer, Markus Sprenger-Haussels, Harriet Wikman, Inger R. Bergheim, Vera Kloten, Ed Schuuring, Michael R. Speicher, and Ellen Heitzer. 2020. "Technical Evaluation of Commercial Mutation Analysis Platforms and Reference Materials for Liquid Biopsy Profiling" Cancers 12, no. 6: 1588. https://doi.org/10.3390/cancers12061588

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