Detection of Overlooked Rare EGFR Mutations in Non-small Cell Lung Cancer Using Multigene Testing.

Area of Science:

• Oncology
• Genetics
• Molecular Diagnostics

Background:

• Precision oncology for non-small cell lung cancer (NSCLC) faces challenges in identifying rare driver mutations.
• The Oncomine Dx Target Test Multi-CDx System (ODxTT) is widely used in Japan for NSCLC genetic testing.
• This study investigates potential overlooked druggable epidermal growth factor receptor (EGFR) mutations by ODxTT.

Purpose of the Study:

• To evaluate if the ODxTT system misses actionable EGFR mutations in NSCLC patients.
• To identify the frequency and types of EGFR mutations overlooked by ODxTT.
• To assess the clinical significance of these missed mutations.

Main Methods:

• Retrospective analysis of 82 non-small cell lung cancer (NSCLC) adenocarcinoma cases initially reported as mutation-negative by ODxTT.
• Targeted sequencing of EGFR exons 18-21 using binary alignment map files.
• Pathological significance of identified mutations assessed using the ClinVar database.

Main Results:

• Ten actionable EGFR mutations (exons 19 and 18) were identified in 12.2% of initially negative cases.
• Detection rates varied among other common genetic tests: Cobas EGFR Mutation Test v2 (3/10), Lung Cancer Compact Panel (6/10), Amoy Dx (0/10).
• Five patients received EGFR tyrosine kinase inhibitor (TKI) therapy, showing partial response (3), stable disease (1), or progressive disease (1).

Conclusions:

• ODxTT failed to detect 10 actionable EGFR mutations in a significant proportion of NSCLC cases.
• Comprehensive genomic profiling is crucial for early and accurate identification of EGFR mutations in suspected cases.
• Timely detection of actionable mutations can guide targeted therapy selection in NSCLC treatment.