External Quality Assessment on Molecular Tumor Profiling with Circulating Tumor DNA-Based Methodologies Routinely Used in Clinical Pathology within the COIN Consortium.

Autor:	van der Leest P; Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.; Department of Laboratory Medicine, Netherlands Cancer Institute, Amsterdam, the Netherlands., Rozendal P; Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Hinrichs J; Department of Pathology, Symbiant B.V., Alkmaar, the Netherlands., van Noesel CJM; Department of Pathology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, the Netherlands., Zwaenepoel K; Department of Pathology, Antwerp University Hospital, University of Antwerp, Edegem, Belgium., Deiman B; Clinical Laboratory, Catharina Hospital Eindhoven, Eindhoven, the Netherlands.; Institute for Complex Molecular Systems, Laboratory of Chemical Biology, Eindhoven University of Technology, Eindhoven, the Netherlands.; Department of Biomedical Engineering, Laboratory of Chemical Biology, Eindhoven University of Technology, Eindhoven, the Netherlands.; Expert Center Clinical Chemistry Eindhoven, Eindhoven, the Netherlands., Huijsmans CJJ; Pathologie-DNA, Laboratory for Molecular Diagnostics, Location Jeroen Bosch Hospital, 's-Hertogenbosch, the Netherlands., van Eijk R; Department of Pathology, Leiden University Medical Centre, Leiden, the Netherlands., Speel EJM; Department of Pathology, GROW-School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, the Netherlands., van Haastert RJ; Department of Clinical Chemistry, St. Antonius Hospital, Nieuwegein, the Netherlands., Ligtenberg MJL; Department of Human Genetics, Radboud Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, the Netherlands.; Department of Pathology, Radboud Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, the Netherlands., van Schaik RHN; Department of Clinical Chemistry, Erasmus MC University Medical Center, Rotterdam, the Netherlands., Jansen MPHM; Department of Medical Oncology, Laboratory of Translational Genomics, Erasmus MC University Medical Center, Rotterdam, the Netherlands., Dubbink HJ; Department of Pathology, Erasmus MC University Medical Center, Rotterdam, the Netherlands., de Leng WW; Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands., Leers MPG; Department of Clinical Chemistry & Hematology, Zuyderland Medical Center, Heerlen, the Netherlands., Tamminga M; Department of Pulmonary Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., van den Broek D; Department of Laboratory Medicine, Netherlands Cancer Institute, Amsterdam, the Netherlands., van Kempen LC; Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.; Department of Pathology, Antwerp University Hospital, University of Antwerp, Edegem, Belgium., Schuuring E; Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Jazyk:	angličtina
Zdroj:	Clinical chemistry [Clin Chem] 2024 May 02; Vol. 70 (5), pp. 759-767.
DOI:	10.1093/clinchem/hvae014
Abstrakt:	Background: Identification of tumor-derived variants in circulating tumor DNA (ctDNA) has potential as a sensitive and reliable surrogate for tumor tissue-based routine diagnostic testing. However, variations in pre(analytical) procedures affect the efficiency of ctDNA recovery. Here, an external quality assessment (EQA) was performed to determine the performance of ctDNA mutation detection work flows that are used in current diagnostic settings across laboratories within the Dutch COIN consortium (ctDNA on the road to implementation in The Netherlands). Methods: Aliquots of 3 high-volume diagnostic leukapheresis (DLA) plasma samples and 3 artificial reference plasma samples with predetermined mutations were distributed among 16 Dutch laboratories. Participating laboratories were requested to perform ctDNA analysis for BRAF exon 15, EGFR exon 18-21, and KRAS exon 2-3 using their regular circulating cell-free DNA (ccfDNA) analysis work flow. Laboratories were assessed based on adherence to the study protocol, overall detection rate, and overall genotyping performance. Results: A broad range of preanalytical conditions (e.g., plasma volume, elution volume, and extraction methods) and analytical methodologies (e.g., droplet digital PCR [ddPCR], small-panel PCR assays, and next-generation sequencing [NGS]) were used. Six laboratories (38%) had a performance score of >0.90; all other laboratories scored between 0.26 and 0.80. Although 13 laboratories (81%) reached a 100% overall detection rate, the therapeutically relevant EGFR p.(S752_I759del) (69%), EGFR p.(N771_H773dup) (50%), and KRAS p.(G12C) (48%) mutations were frequently not genotyped accurately. Conclusions: Divergent (pre)analytical protocols could lead to discrepant clinical outcomes when using the same plasma samples. Standardization of (pre)analytical work flows can facilitate the implementation of reproducible liquid biopsy testing in the clinical routine. (© Association for Diagnostics & Laboratory Medicine 2024.)
Databáze:	MEDLINE
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