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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Prediction models may be applied to estimate the plasma mutation load for diagnostic or research purposes. Mutant allele frequencies were calculated from the submitted depth of coverage data from NGS Table 5. The authors suggested that method sensitivity correlates with diagnostic accuracy. Careful mtuation is particularly important for p. For the cobas assay, mutatioon mean, standard deviation, coefficient of variation CVmedian value, minimum value, and maximum value of data from cobsa peer group and the standard deviation index of the data from the laboratory were provided in the evaluation reports.

Fourteen laboratories received two identical panels of 27 single-blinded plasma samples. From November to Juneseven clinical diagnostic laboratories participated in the EQA program. 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.

In the era of companion diagnostics, more mutations will be used as predictive markers to determine patient eligibility for molecular-targeted therapies. External quality assessment EQA is a way to standardize interlaboratory results and to monitor and teet testing processes across laboratories [ 10 ].

The cobas® EGFR Mutation Test

We performed a ccobas external quality assurance EQA scheme to harmonize circulating tumor DNA testing among laboratories. Therefore, highly sensitive methodologies have been developed to detect low abundance epidermal growth factor receptor EGFR mutations, including p.

There was sufficient coverage at all target mutations to detect variants with allele frequencies of 0. TM and exon 20 insertion mutations were not detected in LOD level 4 material by any of the laboratories.


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

In our validation experiment using the Oncomine Lung cfDNA Assay, all mutations were detected in level 4 material mutatino the coverage depth was more than ,X. Subscribe to Table of Contents Alerts. The fraction of tumor-derived cell-free DNA cfDNA in blood plasma varies according to tumor stage, tumor burden, vascularization of the tumor, biological features of the tumor such as apoptotic rate, and the metastatic potential of the cancer cells [ 2 ].

All targeted mutations were called in levels 1—4 materials at similar allele frequencies to what were expected. Plasma EGFR genotyping methods by laboratories participating in pilot external quality assurance.

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

TM and 70,X for p. The number of reactions per test method among participating laboratories was rgfr Individual laboratories should optimize NGS performance to maximize clinical utility. In AprilEQA materials were made and distributed to each laboratory. Each laboratory director requested the amount of EQA material needed according to the number of methods planned for plasma EGFR testing.

BioMed Research International

TM and exon 20 insertion mutations were not detected in level 3 material unacceptable result. TM HDp. Previous studies reported that it is challenging to detect the p.

When a mutation was detected, semiquantitative index SQI values for each mutation are reported automatically by the software using the observed threshold cycle for the target mutation. It was unclear whether unacceptable responses were due to the performance of specific NGS methods or the laboratory. Materials and Methods 2. Among seven laboratories, only six laboratories had a positive result for exon 19 deletion detection rate NGS generally requires more time than IVD, although it differs depending on batch constitution and the platform used.

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


Larger trial including more genotyping platforms ccobas digital PCR with our sample preparation protocol is worthy of further investigation. TM and exon 20 insertion. To receive news and publication updates for BioMed Research International, enter your email address in the box below. Details are provided in Supplementary Table S2. These test samples had expected mutant allele frequencies of mutatoon. Details are provided in Supplementary Table S1.

The precision of SQI is summarized in Table 4.

Our data and previous reports indicate that high coverage depth is essential to improve the detection of low-level targets [ 1819 ]. Analysis of circulating tumor DNA in plasma may complement limitations of tumor tissue. Moreover, advanced NGS technology enables detection of not only point mutation but also gene fusions and amplifications [ 2223 ].

Data were interpreted by the cobas z software if positive and negative tset showed valid results. Correlations between SQI from cobas assay and mutant allele frequency were analyzed using Spearman rank-correlation test.

Thus, this assay can be used for rapid and reliable plasma ctDNA analysis in clinical diagnostic laboratories.

Correspondence should be addressed to Kyung-A Lee ; ca. Results from two laboratories were consistent with the expected mutant allele frequencies calculated from absolute allele frequencies measured using digital droplet PCR.

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

SQI showed a positive correlation with mutant allele frequency mmutation from digital droplet PCR measurements. 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 ].