TY - JOUR
T1 - Technical Evaluation of Commercial Mutation Analysis Platforms and Reference Materials for Liquid Biopsy Profiling
AU - Weber, Sabrina
AU - Spiegl, Benjamin
AU - Perakis, Samantha O
AU - Ulz, Christine M
AU - Abuja, Peter M
AU - Kashofer, Karl
AU - Leest, Paul van der
AU - Azpurua, Maria Aguirre
AU - Tamminga, Menno
AU - Brudzewsky, Dan
AU - Rothwell, Dominic G
AU - Mohan, Sumitra
AU - Sartori, Alexander
AU - Lampignano, Rita
AU - Konigshofer, Yves
AU - Sprenger-Haussels, Markus
AU - Wikman, Harriet
AU - Bergheim, Inger R
AU - Kloten, Vera
AU - Schuuring, Ed
AU - Speicher, Michael R
AU - Heitzer, Ellen
PY - 2020/6/16
Y1 - 2020/6/16
N2 - 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.
AB - 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.
U2 - 10.3390/cancers12061588
DO - 10.3390/cancers12061588
M3 - Article
C2 - 32560092
VL - 12
SP - 1
EP - 16
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 6
M1 - 1588
ER -