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Updated: Dec 20, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Molecular Diagnostics in Non-Small Cell Lung Carcinoma
1Department of Pathology, Harvard Medical School, Boston, Massachusetts.
Abstract:
Current clinical practice guidelines recognize EGFR, BRAF, ALK, and ROS1 as essential molecular biomarkers, and a host of other genetic alterations as emerging biomarkers for non-small cell lung carcinoma patients. The available approaches to detecting relevant alterations in these genes are diverse and often complementary. Laboratories have increasingly migrated away from a "single-gene test" approach, embracing assays that incorporate panels of genes capable of detecting a diverse set of alterations. The adoption of next generation sequencing (NGS) techniques has driven this shift; however, the approach to incorporation of NGS varies greatly between practices. Choice of molecular diagnostics assay, be it single-gene or NGS-based panel, will be driven by cost, urgency, clinical and laboratory focus, and professional considerations. Preanalytic factors including operator expertise, sample type and choice of fixative, and postanalytic factors including informatics pipeline and approaches to variant reporting have a significant impact on the quality of molecular diagnostics results. There is no real "one-size-fits-all" test for genomic profiling for lung cancer; clinicians and laboratorians must be prepared to offer a diverse set of assays in order to address turnaround time requirements and optimize detection of critical but difficult-to-detect tumor alterations such as gene fusions.
Insights
Molecular profiling for lung cancer is shifting towards comprehensive gene panels, including next-generation sequencing (NGS), moving beyond single-gene tests. Assay selection depends on various factors, emphasizing no single best method for all non-small cell lung carcinoma patients.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genomics
Background:
- Essential molecular biomarkers (EGFR, BRAF, ALK, ROS1) and emerging genetic alterations are crucial for non-small cell lung carcinoma (NSCLC) patient management.
- Traditional single-gene testing is being replaced by comprehensive gene panels for broader alteration detection.
Purpose of the Study:
- To review current approaches in molecular diagnostics for NSCLC.
- To discuss the adoption and variability of next-generation sequencing (NGS) techniques.
- To highlight factors influencing the choice between single-gene and NGS-based panel assays.
Main Methods:
- Review of current clinical practice guidelines and diagnostic approaches for NSCLC.
- Discussion of the impact of next-generation sequencing (NGS) adoption.
- Analysis of preanalytic and postanalytic factors affecting molecular diagnostic quality.
Main Results:
- Laboratories are increasingly adopting gene panels over single-gene tests.
- NGS adoption varies significantly across practices.
- Cost, urgency, and clinical focus influence assay selection.
- Preanalytic and postanalytic factors critically impact results quality.
Conclusions:
- There is no universal genomic profiling test for lung cancer.
- Clinicians and laboratorians must offer diverse assays to meet turnaround times and detect challenging alterations like gene fusions.
- Optimizing molecular diagnostics requires careful consideration of assay choice and quality control.
