Discovery of Targetable Genetic Alterations in NSCLC Patients with Different Metastatic Patterns Using a MassARRAY-Based Circulating Tumor DNA Assay

Cells. 2020 Oct 22;9(11):2337. doi: 10.3390/cells9112337.

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.

Keywords: brain metastases; ctDNA; liquid biopsy; lung cancer; mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor*
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Circulating Tumor DNA*
  • Female
  • Genetic Association Studies / methods
  • Genetic Testing
  • Genetic Variation*
  • Humans
  • Liquid Biopsy / methods*
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / genetics*
  • Male
  • Mutation
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prevalence
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Circulating Tumor DNA