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Updated: May 16, 2026
Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
The introduction of systematic genomic testing for patients with non-small-cell lung cancer
Stephanie Cardarella1, Taylor M Ortiz2, Victoria A Joshi3
1Department of Medical Oncology, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Background:
Genomic testing to identify driver mutations that enable targeted therapy is emerging for patients with non-small-cell lung cancer (NSCLC). We report the implementation of systematic prospective genotyping for somatic alterations in BRAF, PIK3CA, HER2, and ALK, in addition to EGFR and KRAS, in NSCLC patients at the Dana-Farber Cancer Institute.
Methods:
Patients with NSCLC were prospectively referred by their providers for clinical genotyping. Formalin-fixed, paraffin embedded tumor samples were analyzed by Sanger sequencing for mutations in selected exons of EGFR, KRAS, BRAF, PIK3CA, and HER2. ALK rearrangements were detected by fluorescence in situ hybridization or immunohistochemistry.
Results:
Between July 1, 2009 and August 1, 2010, 427 specimens from 419 patients were referred for genomic characterization; 344 (81%) specimens were successfully genotyped with a median turnaround time of 31 days (range, 9-155). Of the 344 specimens, 185 (54%) had at least one identifiable somatic alteration (KRAS: 24%, EGFR: 17%, ALK: 5%, BRAF: 5%, HER2: 4%, PIK3CA: 2%). As of August 1, 2011, 63 of 288 advanced NSCLC patients (22%) had received molecularly targeted therapy based on their genotypic results, including 34 of 42 patients (81%) with EGFR mutations, 12 of 15 (80%) with ALK rearrangements, and 17 of 95 (18%) with KRAS, BRAF, or HER2 mutations.
Conclusions:
Large-scale testing for somatic alterations in EGFR, KRAS, BRAF, PIK3CA, HER2, and ALK is feasible and impacts therapeutic decisions. As the repertoire for personalized therapies expands in lung cancer and other malignancies, there is a need to develop new genomics technologies that can generate a comprehensive genetic profile of tumor specimens in a time- and cost-effective manner.
Insights
Systematic genomic testing for non-small cell lung cancer (NSCLC) is feasible and identifies actionable mutations. This approach impacts targeted therapy decisions, improving patient outcomes.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Genomic testing is increasingly vital for identifying driver mutations in non-small cell lung cancer (NSCLC) to guide targeted therapy.
- This study reports the implementation of systematic prospective genotyping for key somatic alterations in NSCLC patients.
Purpose of the Study:
- To implement and evaluate a comprehensive genomic profiling strategy for NSCLC patients.
- To assess the feasibility and impact of routine molecular testing on therapeutic decisions.
Main Methods:
- Prospective referral of NSCLC patients for clinical genotyping.
- Analysis of formalin-fixed, paraffin-embedded tumor samples using Sanger sequencing for EGFR, KRAS, BRAF, PIK3CA, and HER2 mutations.
- Detection of ALK rearrangements via fluorescence in situ hybridization or immunohistochemistry.
Main Results:
- Of 419 patients, 344 (81%) were successfully genotyped with a median turnaround time of 31 days.
- Somatic alterations were identified in 54% of genotyped specimens (KRAS 24%, EGFR 17%, ALK 5%, BRAF 5%, HER2 4%, PIK3CA 2%).
- 22% of advanced NSCLC patients received targeted therapy based on results, with high utilization for EGFR mutations (81%) and ALK rearrangements (80%).
Conclusions:
- Large-scale genomic testing for NSCLC is feasible and directly influences treatment choices.
- The findings support the integration of comprehensive genomic profiling into routine clinical practice for NSCLC.
- Development of efficient and cost-effective genomics technologies is crucial for expanding personalized therapies.
