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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Utility of multigene panel next-generation sequencing in routine clinical practice for identifying genomic
Udit Nindra1,2,3,4, Abhijit Pal1,3, Victoria Bray1
1Department of Medical Oncology, Liverpool Hospital, Sydney, New South Wales, Australia.
Background:
The standard of care in newly diagnosed metastatic non-small cell lung cancer (NSCLC) is to test for aberrations in three genes for driver mutations - ALK, ROS1 and epidermal growth factor receptor (EGFR) - and also for immunohistochemistry to be performed for programmed death-ligand 1 expression level. Next-generation sequencing (NGS), with or without RNA fusion testing, is increasingly used in standard clinical practice to identify patients with potentially actionable mutations. Stratification of NGS mutation tiers is currently based on the European Society of Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT) Tiers I-V and X.
Aim:
Our aim was to analyse NSCLC tumour samples for the prevalence of Tiers I-V mutations to establish guidance for current and novel treatments in patients with metastatic disease.
Methods:
NGS was performed employing the Oncomine Precision Assay (without RNA fusion testing) that interrogates DNA hotspot variants across 45 genes to screen 210 NSCLC tissue samples obtained across six Sydney hospitals between June 2021 and March 2022.
Results:
In our cohort, 161 of 210 (77%) had at least one gene mutation identified, with 41 of 210 (20%) having two or more concurrent mutations. Tier I mutations included 42 of 210 (20%) EGFR mutations (EIA) and five of 210 (3%) MET exon 14 skipping mutations (EIB). Non-Tier I variants included 22 of 210 (11%) KRAS G12C hotspot mutations (EIIB), with a further 47 of 210 (22%) having non-G12C KRAS (EX) mutations. NGS testing revealed an additional 15% of cases with Tier II ESCAT mutations in NSCLC. Forty-six percent of patients also demonstrated potential Tier III and IV mutations that are currently under investigation in early-phase clinical trials.
Conclusions:
In addition to identifying patients with genomic alterations suitable for clinically proven standard-of-care therapeutic options, the 45-gene NGS panel has significant potential in identifying potentially actionable non-Tier 1 mutations that may become future standard clinical practice in NSCLC.
Insights
Next-generation sequencing (NGS) identified common and novel mutations in metastatic non-small cell lung cancer (NSCLC). This analysis aids in guiding current and future treatments for NSCLC patients.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Standard care for metastatic non-small cell lung cancer (NSCLC) involves testing for ALK, ROS1, and EGFR mutations, alongside PD-L1 expression.
- Next-generation sequencing (NGS) is increasingly utilized to detect actionable mutations in NSCLC.
- Mutation tiers are classified using the European Society of Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT).
Purpose of the Study:
- To analyze the prevalence of ESCAT Tiers I-V mutations in NSCLC tumor samples.
- To establish guidance for current and novel treatment strategies in metastatic NSCLC patients.
- To evaluate the utility of a 45-gene NGS panel for comprehensive mutation profiling.
Main Methods:
- Next-generation sequencing (NGS) was performed using the Oncomine Precision Assay.
- The assay interrogated DNA hotspot variants across 45 genes.
- 210 NSCLC tissue samples from six Sydney hospitals (June 2021-March 2022) were analyzed.
Main Results:
- 77% of NSCLC samples (161/210) harbored at least one gene mutation.
- 20% (42/210) had EGFR mutations (Tier I), and 3% (5/210) had MET exon 14 skipping mutations (Tier I).
- Non-Tier I mutations included KRAS G12C (11%) and other KRAS variants (22%). 15% had Tier II mutations, and 46% showed potential Tier III/IV mutations.
Conclusions:
- The 45-gene NGS panel identifies patients eligible for standard-of-care therapies.
- The panel also detects potentially actionable non-Tier 1 mutations for future clinical application.
- This comprehensive approach supports personalized treatment strategies in NSCLC.
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