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Updated: Jun 25, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Comparison of diagnostic performance between Oncomine Dx target test and AmoyDx panel for detecting actionable
Yuki Nagakubo1, Yosuke Hirotsu2, Mona Yoshino1
1Division of Genetics and Clinical Laboratory, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi, Japan.
Abstract:
Companion diagnostic (CDx) tests play important roles in identifying oncogenic driver genes and tailoring effective molecularly targeted therapies for lung cancer patients. In Japan, the Oncomine Dx target test (ODxTT) and the AmoyDx pan lung cancer PCR panel (AmoyDx) are prominent CDx tests and only one of these tests is covered by the domestic insurance system. However, these CDx tests cover different target regions and apply different technologies (ODxTT is amplicon-based next-generation sequencing and AmoyDx is multiplex PCR-based assay), which may lead to missing of actionable mutations affecting patient prognosis. Here, we performed a direct comparison analysis of 1059 genetic alterations of eight driver genes from 131 samples and evaluated the concordance between two CDx tests for detecting actionable variants and fusions. When excluding the eight uncovered variants (ODxTT: two variants, AmoyDx: six variants), the overall percent agreement was 97.6% (1026/1051) with 89.0% of overall positive percent agreement (89/100) and 98.5% of overall negative percent agreement (937/951). Of the 25 discordant genetic alterations, two were undetected despite being covered in the AmoyDx (one EGFR variant and one ROS1 fusion). Furthermore, there were potential false positives in the ODxTT (nine MET exon 14 skippings) and in the AmoyDx (five variants, six ROS1 and three RET fusions). These potential false positives in the AmoyDx likely due to non-specific amplification, which was validated by the unique molecular barcoding sequencing. The ODxTT missed two uncovered EGFR rare variants, which was visually confirmed in the raw sequencing data. Our study provides insights into real-world performance of CDx tests for lung cancer and ensures reliability to advance precision medicine.
Insights
Companion diagnostic tests are crucial for lung cancer precision medicine. Direct comparison of Oncomine Dx and AmoyDx revealed high agreement but also discrepancies, highlighting the need for careful test selection to ensure reliable detection of actionable mutations.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Companion diagnostic (CDx) tests are vital for personalized lung cancer treatment by identifying oncogenic drivers.
- In Japan, Oncomine Dx target test (ODxTT) and AmoyDx pan lung cancer PCR panel (AmoyDx) are key CDx tests, but only one is insured.
- Discrepancies in target regions and technologies between ODxTT and AmoyDx may lead to missed actionable mutations.
Purpose of the Study:
- To directly compare the performance of ODxTT and AmoyDx for detecting actionable genetic alterations in lung cancer.
- To evaluate the concordance between these two prominent CDx tests in a real-world setting.
- To identify potential discrepancies, including false positives and negatives, to ensure diagnostic reliability.
Main Methods:
- Direct comparison analysis of 1059 genetic alterations across eight driver genes in 131 lung cancer samples.
- Evaluation of concordance between ODxTT (amplicon-based NGS) and AmoyDx (multiplex PCR) for actionable variants and fusions.
- Validation of potential false positives in AmoyDx using unique molecular barcoding sequencing.
Main Results:
- High overall percent agreement (97.6%) between ODxTT and AmoyDx, with 89.0% positive and 98.5% negative percent agreement, excluding uncovered variants.
- Discordant results included two missed actionable alterations by AmoyDx (EGFR variant, ROS1 fusion) and potential false positives in both ODxTT (MET exon 14 skippings) and AmoyDx (various variants and fusions).
- Potential false positives in AmoyDx were linked to non-specific amplification, while ODxTT missed rare EGFR variants confirmed in raw sequencing data.
Conclusions:
- This study provides critical insights into the real-world performance and concordance of leading CDx tests for lung cancer in Japan.
- Identified discrepancies underscore the importance of understanding test-specific limitations to avoid missing actionable mutations.
- Ensuring the reliability of CDx test results is essential for advancing precision medicine in lung cancer treatment.
