COBAS EGFR MUTATION TEST PDF

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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TM mutation in relapsed tumors because of tumor heterogeneity [ 6 ]. For the cobas assay, the mean, standard deviation, coefficient of variation CVmedian value, minimum value, and maximum value of data mutstion the peer group and the standard deviation index of the data from the laboratory were provided in the evaluation reports. Unacceptable response rate in pilot external quality assurance scheme. SQI showed a positive correlation with mutant allele frequency derived from digital droplet PCR measurements.

Preparation of EQA Materials 2. However, coverage depth ,utation from two laboratories indicate that more read coverage depth is required to detect low-frequency variants in samples.

In Juneevaluation reports were distributed to participating laboratories. CS resistance mutation [ 20 ] or novel mutations in EGFRas well as other effr, can be identified [ 21 ].

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

Comparison of mutant allelic frequency from two laboratories using different next-generation sequencing platforms. Introduction 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 ].

Plasma EGFR genotyping methods by laboratories participating in pilot external quality assurance. A month after distributing the EQA materials, all results were emailed from each laboratory to an organizing director. We performed a pilot external quality assurance EQA scheme to harmonize circulating tumor DNA testing among laboratories.

EQA is critical for quality assurance and continuous improvement of individual laboratory performance [ 9 ]. Table of Contents Alerts. A limitation of this study is the small number of laboratories that participated, especially laboratories performing NGS.

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The cobas assay generally showed good reproducibility with a CV between 1. In the era of companion diagnostics, more mutations will be used as predictive markers to determine patient eligibility for molecular-targeted therapies.

TM and 70,X for p. 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. Among seven laboratories, only six laboratories had a positive result for exon 19 deletion detection rate The number of reactions per test method among participating laboratories was Published by Elsevier Inc.

Tumor-derived ctDNA often represents a small percentage of the total cfDNA and can be present at allele fractions as low as 0. The precision of SQI is summarized in Table 4. Exon 19 deletion and exon 20 insertion mutations were detected at 0.

All targeted mutations were called in levels 1—4 materials at similar allele frequencies to what were expected. 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 ].

BioMed Research International

LR HDand p. The analytical sensitivities of the cobas assay were not identical for the different target mutations, similar to previous reports [ 1415 ]. This finding is consistent with that of a previous study that evaluated clinical samples with NGS and the cobas assay [ 13 ].

The authors suggested that method sensitivity correlates with diagnostic accuracy. Amplification and detection were performed using the cobas z analyzer Roche Molecular Systems, Inc. Results from two laboratories were consistent with the expected mutant allele frequencies calculated from absolute allele frequencies measured using digital droplet PCR. 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.

Prediction models may be applied to estimate the plasma mutation load for diagnostic or research purposes. This finding is an important issue for detection of p. LR were not detected, despite adequate depth of coverage of the target site compared to other loci.

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

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

In a deep sequencing run, all four quality control samples were sequenced with high median coverage depth of more than 86,X. LOD level 4 material, which had an expected mutant allele frequency of 0.

It was unclear whether unacceptable responses were due to the performance of specific NGS methods or the laboratory. There was sufficient coverage at all target mutations to detect variants with allele frequencies of 0.

For all mutations, SQI values from 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.

TM HDp.

From November to Juneseven clinical diagnostic laboratories participated in the EQA program. Indexed in Science Citation Index Expanded.

The cobas® EGFR Mutation Test

Quantitative results from the cobas assay were positively correlated with allele frequencies derived from digital droplet PCR measurements and showed good reproducibility among laboratories. TM, and d p. Therefore, highly sensitive methodologies have been developed to detect low abundance epidermal growth factor receptor EGFR mutations, including p. 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.

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.

TM and exon 20 insertion mutations were not detected in LOD level 4 material by any of the laboratories.