NCI and Clinical Cancer Research publish a large-scale concordance study of tumor comprehensive genomic profiling across 26 NGS laboratories. Results were very good.
See a blog by Howard McLeod here.
See the full paper by Zane et al., released August 15, here.
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I have not seen the full paper, but I'll include the remarks and the abstract below.
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McLeod
Howard McLeod, Center Director at Center for Precision Medicine and Functional Genomics, shared a post on LinkedIn:
- “The National Cancer Institute (NCI) MATCH study gave an opportunity to assess concordance of comprehensive genomic profiling across 11 commercial and 14 academic laboratories (with the NCI central lab being the standard).
- As many of us have seen in practice, high concordance for SNV, insert, deletion, and copy number variants in therapeutically relevant driver genes for NGS across the labs (not as good for hybridization capture assays).
- Gives confidence for using the NGS lab that gives you the genes you need, at the turn around time that is needed.”
- Title: A Concordance Study among 26 NGS Laboratories Participating in the NCI Molecular Analysis for Therapy Choice Clinical Trial Available to Purchase
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Zane
Purpose:
NCI selected a network of Clinical Laboratory Improvement Amendments–certified laboratories performing routine next-generation sequencing (NGS) tumor testing to identify patients for the NCI Molecular Analysis for Therapy Choice (NCI-MATCH) trial. This large network provided a unique opportunity to compare variant detection and reporting between a wide range of testing platforms.
Experimental Design:
Twenty-eight NGS assays from 26 laboratories within the NCI-MATCH Network, including the NCI-MATCH central laboratory (CL) and 11 commercial and 14 academic designated laboratories (DL), were used for this study. DNA from eight cell lines and two clinical samples were sequenced. Pairwise comparisons in variant detection and reporting between each DL and CL were performed for single-nucleotide variant, insertion and deletion, and copy-number variant classes.
Results:
We observed high concordance in variant detection between CL and DL for single-nucleotide variants and insertions and deletions [average positive agreement (APA) > 95.4% for all pairwise comparisons] but lower concordance for variant reporting after analysis pipeline filtering.
We observed much higher agreement between CL and assays using amplification as the target enrichment method (84.2% < APA ≤ 95.7%, average APA = 88.7%) than other assays using hybridization capture (69.7% < APA ≤ 93.8%, average APA = 77.4%) due to blacklisting of actionable variants in low complexity regions.
For copy-number variant reporting, we observed high agreement (APA > 82%) except between CL and two assays (APA = 76.9% and 71.4%) due to differences in estimation of copy numbers. Notably, for all variants, differences in variant interpretation also contributed to reporting discrepancies.
Conclusions:
This study indicates that different NGS tumor profiling tests currently in widespread clinical use achieve high concordance between assays in variant detection. For variant reporting, observed discrepancies are mainly introduced during the bioinformatic analysis.
