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Although we have experienced some cases with discordant results between the Oncomine Dx target test (ODxTT) and conventional single gene tests for detecting EGFR alterations, the clinical efficacy of EGFR-TKIs in these discordant cases remains little known. We retrospectively reviewed consecutive patients with non-small-cell lung cancer whose FFPE samples were simultaneously submitted for the ODxTT, and a PNA-LNA PCR clamp test. We evaluated the clinical efficacy of EGFR-TKIs in patients with discordant results between the two tests, focusing on the common EGFR mutations. Among 444 successful results, 10 patients had discordant results for common EGFR mutations (9 Ex 19 deletion and 1 Ex 21 L858R mutation), and all of these were detected only by the PNA-LNA PCR clamp test. Among six discordant cases treated with EGFR-TKI, the mutations detected in 3 patients were not included in the list of detectable variants that are reportable by the ODxTT, while the mutations detected in the other 3 patients were included in the list. For all three discordant cases harboring the mutations not reportable by the ODxTT, good clinical responses were demonstrated. However, among the other three discordant cases harboring the mutations reportable by the ODxTT, only one patient had a clinical response with short duration. Among the discordant cases for common EGFR mutations between the ODxTT and the conventional single gene test, there are a certain number of suitable patients responsive to EGFR-TKIs, especially when the cause of the discordant results comes from the difference in the range of detectable variants that are reportable between the tests. [ABSTRACT FROM AUTHOR]

The lower success rate of the ODxTT for lobectomy samples in the early period was due to invalid RNA analysis results. Therefore, we experienced invalid RNA analysis results due to a failure to meet the RNA sample QC (quality control) metrics, especially in lobectomy samples. Keywords: genetic analysis; lobectomy; next-generation sequencing; non-small cell lung cancer EN genetic analysis lobectomy next-generation sequencing non-small cell lung cancer 887 890 4 08/19/21 20210901 NES 210901 The Oncomine Dx Target Test (ODxTT) (Ion Torrent PGM Dx Sequencer; Thermo Fisher Scientific) is a next-generation sequencing panel, which detects 46 genes on DNA and RNA isolated from formalin-fixed and paraffin-embedded (FFPE) specimens using the Ion PGM™ Dx System. [Extracted from the article]

Background: Next‐generation sequencing (NGS) has been implemented in clinical oncology to analyze multiple genes and to guide targeted therapy; however, little is known about the performance of the Oncomine Dx Target Test compared with conventional single gene tests for detecting EGFR mutations. The objective of this study was to evaluate the performance of the Oncomine Dx Target Test compared with a PNA‐LNA PCR clamp test to detect EGFR mutations. Methods: We retrospectively reviewed consecutive patients with non‐small cell lung cancer (NSCLC) from whom FFPE samples were simultaneously submitted for the Oncomine Dx Target Test, and a PNA‐LNA PCR clamp test using the same specimen. We subsequently compared the analysis success rates and detection rates between the two tests. Results: A total of 116 samples were identified. The success rates and detection rates of EGFR mutations in the total number of samples were 90% and 28%, respectively for the Oncomine Dx Target Test, and 100% and 35% for the PNA‐LNA PCR clamp test. The Oncomine Dx Target Test was unable to analyze three samples (2%) due to the samples not passing the nucleic acid concentration threshold, and nine (8%) samples had invalid results. The exon 19 deletion was not detected by the Oncomine Dx Target Test in four cases (4%). Conclusions: The analytical performance of the Oncomine Dx Target Test analysis for EGFR mutations may not be comparable with conventional single gene tests due to both invalid and false‐negative results. Key points: Significant findings of the study: The success rate of the Oncomine Dx Target Test was significantly lower than the PNA‐LNA PCR clamp test.Among the samples successfully analyzed, four exon 19 deletions were not detected by the Oncomine Dx Target Test. What this study adds: The analytical performance of the Oncomine Dx Target Test may not be comparable with conventional single gene tests.We should revise the sampling procedures, and review the sample quality assessment methods, to improve the analytical performance. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung adenocarcinomas caused by (L858R) somatic mutation in the epidermal growth factor receptor (EGFR) show good therapeutic response to tyrosine kinase inhibitors. These tumors develop resistance to therapy mainly after acquired T790M mutation. However, whether the T790M mutation occurred before or after therapy is unknown. To demonstrate this, we developed mice with tetracycline-inducible lung-specific expression of the full-length genomic DNA of the human epidermal growth factor receptor containing an L858R mutation or both L858R and T790M mutations and evaluated de novo T790M mutation in untreated transgenic mice carrying a single L858R EGFR mutation. The results showed that lung tumors spontaneously acquire T790M mutation without any drug-related selective pressure. Background: Lung cancer is the leading cause of mortality for cancer worldwide. A point mutation in exon 21 of the epidermal growth factor receptor resulting in the substitution of arginine for leucine at position 858 (L858R) is a frequent cause of lung adenocarcinoma. Tyrosine kinase inhibitors are effective for treating patients with lung cancer associated with mutant epidermal growth factor receptors but most tumors become resistant shortly after treatment. The substitution of methionine for threonine at position 790 (T790M) on exon 20 is the most frequently acquired mutation leading to resistance to tyrosine kinase inhibitors. Whether the T790M mutation occurred after tyrosine kinase inhibitor therapy or it already existed before therapy is unclear. Methods: Here, we developed mice with tetracycline-inducible lung-specific expression of the full-length genomic DNA of the human epidermal growth factor receptor containing an L858R mutation or both L858R and T790M mutations and evaluated de novo T790M mutation in untreated transgenic mice carrying a single L858R EGFR mutation. Results: The L858R mutation-associated lung adenocarcinoma acquired de novo T790 mutation without previous therapy. Conclusions: The results of this study suggest that lung tumors may spontaneously acquire T790M mutations without any drug-related selective pressure. [ABSTRACT FROM AUTHOR]