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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All eight measurements of Test 4 material detected the exon 19 deletion. LR mutations were not detected, despite the fact that total read coverage depth was not lower for these loci than other loci 65,X for p.

TM detection in the setting of relapse. All specificities were Unacceptable response rate in pilot external quality assurance scheme. LOD level 4 material, which had an expected mutant allele frequency of 0. The precision of SQI is summarized in Table 4.

LeuArg variants for the lowest target copies. Liquid biopsies to genotype the epidermal growth factor receptor EGFR for targeted therapy have been implemented in clinical decision-making in the field of lung cancer, but harmonization of detection methods is still scarce among clinical laboratories. Copy numbers and frequencies of mutant alleles are provided in Supplementary Table S3.

These test samples had expected mutant allele frequencies of 3. 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 ].

LR in LOD level 4 material. Among seven laboratories, only six laboratories had a positive result for exon 19 deletion detection rate TM testing included pyrosequencing, digital PCR, and several allele-specific PCR platforms, using four levels of spiked materials [ 25 ]. External quality assessment EQA is a way to standardize interlaboratory results and to monitor and improve testing processes across laboratories [ 10 ].


Mutant allele frequencies were calculated from the submitted depth of coverage data from NGS Table 5. The workflow of the study process is shown in Supplementary Figure S1. For the cobas assay, the mean, standard deviation, coefficient of variation CVmedian value, minimum value, and maximum value of data from the peer group and the standard deviation index of the data from the laboratory were provided in the evaluation reports.

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. All values were two-sided, and values less than 0. Table of Contents Alerts. Submitted qualitative results were evaluated as acceptable positive for expected mutations or negative for unexpected mutations or unacceptable negative for expected mutations or positive for unexpected mutationsaccording to the manufactured and validated target mutations in this study Table 1 and Supplementary Table S2.

Abstract Liquid biopsies to genotype the epidermal growth factor receptor EGFR for targeted therapy have been implemented in clinical decision-making in the field of lung cancer, but harmonization of detection methods is still scarce among clinical laboratories. Exon 19 deletion and exon 20 insertion mutations were detected at 0.

This difference in assay performance according to target mutation might be due to the assay design and characteristics of the target regions [ 1415 ].

BioMed Research International

Published by Elsevier Inc. The cobas assay generally showed good reproducibility with a CV between 1. A limitation of this study is the small number of laboratories that participated, especially laboratories performing NGS. For all other variants, sensitivities varied between Coefficients of variation indicated good intralaboratory and interlaboratory repeatability and reproducibility but increased for decreasing fobas.


Details are provided in Supplementary Table S1. In AprilEQA materials were made and distributed to each laboratory. From November to Juneseven clinical diagnostic laboratories participated in the EQA program.

We performed a pilot external quality assurance EQA scheme to harmonize circulating tumor DNA testing among laboratories. 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

Lowest sensitivities were obtained for the c. Quantitative results from the cobas assay were positively correlated with allele frequencies derived from digital droplet PCR measurements and showed good reproducibility among laboratories.

Moreover, advanced NGS technology enables detection of not only point mutation but also gene fusions and amplifications [ 2223 ].

Seven of nine cobas assays Individual laboratories should optimize NGS performance to maximize clinical utility. In Juneevaluation reports were distributed to participating laboratories. Although we used limited number of methods of two NGS and one IVD platform, we suggested more delicate means of EQA workflow tailored to ctDNA testing, using strictly designed low-level materials to assess assay sensitivity and precision in individual laboratories.

Mutatiion than for p.