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Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
Published on: October 18, 2013
Clinical utility of the Oncomine Dx Target Test multi-CDx system and the possibility of utilizing those original
Ayaka Saito1, Hideki Terai1,2, Tae-Jung Kim3
1Department of Internal Medicine (Pulmonary Medicine), School of Medicine, Keio University, Tokyo, Japan.
Background:
Companion diagnostic tests play a crucial role in guiding treatment decisions for patients with non-small cell lung cancer (NSCLC). The Oncomine Dx Target Test (ODxTT) Multi-CDx System has emerged as a prominent companion diagnostic method. However, its efficacy in detecting driver gene mutations, particularly rare mutations, warrants investigation.
Aims:
This study aimed to assess the performance of the ODxTT in detecting driver gene mutations in NSCLC patients. Specifically, we aimed to evaluate its sensitivity in detecting epidermal growth factor receptor (EGFR) mutations, a key determinant of treatment selection in NSCLC.
Materials And Methods:
We conducted a retrospective analysis of NSCLC patients who underwent testing with the ODxTT at Keio University Hospital between May 2020 and March 2022. Patient samples were subjected to both DNA and RNA tests. Driver gene mutation status was assessed, and instances of missed mutations were meticulously examined.
Results:
Of the 90 patients, five had nucleic acid quality problems, while 85 underwent both DNA and RNA tests. Driver gene mutations were detected in 56/90 (62.2%) patients. Of the 34 patient specimens, driver mutations were not detected using the ODxTT; however, epidermal growth factor receptor (EGFR) mutations were detected using polymerase chain reaction-based testing in two patients, and a KRAS mutation was detected by careful examination of the sequence data obtained using the ODxTT in one patient. For the above three cases, carefully examining the gene sequence information obtained using the ODxTT could identify driver mutations that were not mentioned in the returned test results. Additionally, we confirmed comparable instances of overlook results for EGFR mutations in the dataset from South Korea, implying that this type of oversight could occur in other countries using the ODxTT. EGFR mutation was missed in ODxTT in Japan (6.3%, 2/32), South Korea (2.0%, 1/49), and overall (3.7%, 3/81).
Conclusion:
Even if sufficient tumor samples are obtained, rare EGFR mutations (which are excluded from the ODxTT's genetic mutation list) might not be detected using the current ODxTT system due to the program used for sequence analysis. However, such rare EGFR mutations can still be accurately detected on ODxTT's sequence data using next-generation sequencing.
Insights
The Oncomine Dx Target Test (ODxTT) may miss rare EGFR mutations in non-small cell lung cancer (NSCLC) patients. Re-analysis of ODxTT sequence data can identify these overlooked driver mutations.
Area of Science:
- Oncology
- Genetics
- Molecular Diagnostics
Background:
- Companion diagnostics are vital for non-small cell lung cancer (NSCLC) treatment selection.
- The Oncomine Dx Target Test (ODxTT) is a widely used diagnostic system.
- The ability of ODxTT to detect rare driver gene mutations requires further evaluation.
Purpose of the Study:
- To assess the performance of the Oncomine Dx Target Test (ODxTT) in identifying driver gene mutations in NSCLC.
- To specifically evaluate ODxTT's sensitivity for detecting epidermal growth factor receptor (EGFR) mutations.
- To investigate the potential for ODxTT to miss rare mutations.
Main Methods:
- Retrospective analysis of 90 NSCLC patients tested with ODxTT at Keio University Hospital (May 2020 - March 2022).
- Samples underwent both DNA and RNA testing.
- Driver gene mutation status was assessed, with a focus on identifying missed mutations.
Main Results:
- Driver mutations were detected in 62.2% of patients (56/90).
- ODxTT failed to detect mutations in 34 specimens, but subsequent analysis revealed EGFR mutations in two and a KRAS mutation in one patient.
- EGFR mutations were missed by ODxTT in 3.7% of cases overall, with similar findings in South Korean datasets, indicating potential for cross-border oversight.
Conclusions:
- The ODxTT system may not detect rare EGFR mutations due to its sequence analysis program, even with adequate samples.
- These rare mutations, excluded from the ODxTT's standard list, can be identified by re-analyzing ODxTT sequence data using next-generation sequencing.
- This highlights the importance of reviewing raw sequence data for comprehensive mutation detection in NSCLC.
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