Here we review one of these companion tests, the Roche cobas® EGFR mutation test v2, from a methodological point of view, also exploring its. “The cobas® EGFR Mutation Test v2 is a companion diagnostic test that supports IRESSA® as an additional therapeutic option for patients and. The U.S. Food and Drug Administration (FDA) recently approved the cobas EGFR Mutation Test v2 as a companion diagnostic test with gefitinib.

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This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Seven of nine cobas assays Dots in the figure represent negative measurement ND or the SQI value of the positive measurement for a p. All results obtained using the cobas assay were concordant except for detection of EGFR exon 19 deletion and p.

Circulating tumor DNA ctDNA carries the same molecular alterations as the tumor itself and can be used to select treatment, assess the emergence of drug resistance, and monitor lung cancer patients in routine clinical practice [ 1 ]. TM, and d p.

BioMed Research International

In our pilot EQA, the cobas assay showed a higher detection rate and lower imprecision for exon 19 deletion and p. Table of Contents Alerts. Torrent Suite software provides molecular coverage depth as well as read coverage depth at target bases to increase detection sensitivity for low-frequency variants [ 1112 ].

Using NGS, rare e. Thus, this assay can be used for rapid and reliable plasma ctDNA analysis in clinical diagnostic laboratories. In the present study, we confirmed the LODs of the cobas assay for each target mutation. These test samples had expected mutant allele frequencies of 3. External quality assessment EQA is a way to standardize interlaboratory results twst to monitor and improve testing processes across laboratories [ 10 ].

There was sufficient coverage at all target mutations to detect variants with allele frequencies of 0. Unacceptable response rate in pilot external quality assurance scheme.


TM testing included pyrosequencing, digital PCR, and several allele-specific PCR platforms, using four levels egdr spiked materials [ 25 ].

Liquid biopsies to genotype the epidermal growth factor receptor EGFR for targeted therapy have been implemented in mutatioh decision-making in the field of lung cancer, but harmonization of detection methods is still scarce among clinical laboratories.

Correspondence should be addressed to Kyung-A Lee ; ca. The number of reactions per test method among participating laboratories was SQI showed a positive correlation with mutant allele frequency derived from digital droplet PCR measurements.

Analytical performance of the cobas EGFR mutation assay for Japanese non-small-cell lung cancer.

Careful interpretation is particularly important for p. Correlations between SQI from cobas assay and mutant allele frequency were analyzed using Spearman rank-correlation test. Therefore, highly sensitive methodologies have been developed to detect low abundance epidermal growth factor receptor EGFR mutations, including p. It was unclear whether egfrr responses were due to the performance of specific NGS methods or the laboratory.

TM and exon 20 insertion mutations were not detected in LOD level 4 material by any of the laboratories. None of the four target mutations were detected in level 4 material.

Individual laboratories should optimize NGS performance to maximize clinical utility. Larger trial including more genotyping platforms including digital PCR with our sample preparation protocol is worthy of further investigation.

Subscribe to Table of Contents Alerts. Lowest sensitivities were obtained for the c. In Juneevaluation reports were distributed to participating laboratories.

A limitation of this study is the small number of laboratories that participated, especially laboratories performing NGS. Among seven mugation, only six laboratories had a positive result for exon 19 deletion detection rate TM and exon 20 insertion mutations were not detected in level 3 material unacceptable result. Quantitative results from the cobas assay were positively correlated with allele frequencies derived from digital droplet Mutztion measurements and showed good reproducibility among laboratories.

Recently, Haselmann et al. LR mutations cogas not detected, despite the fact that total read coverage depth was not lower for these loci than other loci 65,X for p. In a deep sequencing run, all four quality control samples were sequenced with high median coverage depth of more than 86,X. All specificities were TM HDp. TM and exon 20 insertion. Exon 19 deletion tdst exon 20 insertion mutations were detected at 0.


For all mutations, SQI values from the cobas assay exhibited a strong positive correlation with the expected mutant allele frequencies derived from mutattion droplet PCR measurements Spearman mutahion coefficient, 0.

The cobas assay generally showed good reproducibility with a CV between 1. Introduction Circulating tumor DNA ctDNA carries the same molecular alterations as the tumor dgfr and can be used to select treatment, assess the emergence of drug resistance, and monitor lung cancer patients in routine clinical practice [ 1 ].

TM detection in the setting of relapse. Moreover, advanced NGS technology enables detection of not only point mutation but also gene fusions and amplifications [ 2223 ]. Samples were wild type or spiked with plasmid DNA to contain seven common EGFR variants at six predefined concentrations from 50 to copies per milliliter.

The cobas® EGFR Mutation Test

Published by Elsevier Inc. All eight measurements of Test 4 material detected the exon 19 deletion.

All values were two-sided, and values less than 0. As a mutaton, rigorous quality controls to avoid inappropriate patient treatment will become increasingly important in clinical diagnostic laboratories. We performed a pilot external quality assurance EQA scheme to harmonize circulating tumor DNA testing among laboratories.

EQA is critical for quality assurance muutation continuous improvement of individual laboratory performance [ 9 ]. A month after distributing the EQA materials, all results were emailed from each laboratory to an organizing director.

LR than for p.