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Updated: Dec 3, 2025
Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
Published on: October 18, 2013
Discovery of Targetable Genetic Alterations in NSCLC Patients with Different Metastatic Patterns Using a
Yassine Belloum1, Melanie Janning1,2,3,4, Malte Mohme5
1Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Abstract:
Circulating tumor DNA (ctDNA) has shown great promise as a minimally invasive liquid biopsy for personalized cancer diagnostics especially among metastatic patients. Here, we used a novel sensitive assay to detect clinically relevant mutations in ctDNA in blood plasma from metastatic non-small cell lung cancer (NSCLC) patients, including patients with a limited oligo-brain metastatic disease. We analyzed 66 plasma samples from 56 metastatic NSCLC patients for 74 hotspot mutations in five genes commonly mutated in NSCLC using a novel MassARRAY-based lung cancer panel with a turnaround time of only 3 days. Mutations in plasma DNA could be detected in 28 out of 56 patients (50.0%), with a variant allele frequency (VAF) ranging between 0.1% and 5.0%. Mutations were detected in 50.0% of patients with oligo-brain metastatic disease, although the median VAF was lower (0.4%) compared to multi-brain metastatic patients (0.9%) and patients with extra-cranial metastatic progression (1.2%). We observed an overall concordance of 86.4% (n = 38/44) for EGFR status between plasma and tissue. The MassARRAY technology can detect clinically relevant mutations in plasma DNA from metastatic NSCLC patients including patients with limited, oligo-brain metastatic disease.
Insights
Detecting circulating tumor DNA (ctDNA) mutations in blood plasma shows promise for diagnosing metastatic non-small cell lung cancer (NSCLC). A novel assay identified mutations in 50% of NSCLC patients, including those with brain metastases.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Circulating tumor DNA (ctDNA) offers a minimally invasive approach for cancer diagnostics, particularly in metastatic patients.
- Non-small cell lung cancer (NSCLC) management benefits from precise molecular profiling for personalized treatment strategies.
- Liquid biopsies are emerging as valuable tools for detecting actionable mutations in advanced cancers.
Purpose of the Study:
- To evaluate a novel sensitive assay for detecting clinically relevant mutations in ctDNA from metastatic NSCLC patients.
- To assess the utility of ctDNA analysis in patients with limited oligo-brain metastatic disease.
- To determine the turnaround time and concordance of ctDNA mutation detection compared to tissue biopsies.
Main Methods:
- Analysis of 66 plasma samples from 56 metastatic NSCLC patients.
- Utilized a novel MassARRAY-based lung cancer panel to screen for 74 hotspot mutations in five key genes.
- Assessed variant allele frequency (VAF) and concordance with tissue biopsy results for EGFR mutations.
Main Results:
- Mutations were detected in 50.0% (28/56) of metastatic NSCLC patients, with VAFs ranging from 0.1% to 5.0%.
- ctDNA mutations were identified in 50.0% of patients with oligo-brain metastases, showing lower median VAF compared to other metastatic sites.
- An 86.4% concordance rate was observed for EGFR status between plasma ctDNA and tissue biopsies.
Conclusions:
- The novel MassARRAY-based assay effectively detects clinically relevant ctDNA mutations in metastatic NSCLC patients.
- This approach is valuable for patients with limited oligo-brain metastatic disease, offering a less invasive diagnostic option.
- ctDNA analysis via this sensitive assay shows high concordance with tissue genotyping, supporting its role in personalized cancer care.
