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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
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Single Circulating-Tumor-Cell-Targeted Sequencing to Identify Somatic Variants in Liquid Biopsies in Non-Small-Cell
Mouadh Barbirou1, Amanda Miller1, Yariswamy Manjunath2,3
1Center for Biomedical Informatics, Department of Health Management and Informatics, School of Medicine, University of Missouri, Columbia, MO 65212, USA.
Current Issues in Molecular Biology
|June 20, 2022
Summary
Detecting somatic variants in single circulating tumor cells (CTCs) from non-small-cell lung cancer (NSCLC) patients using targeted next-generation sequencing (NGS) reveals key mutations for precision oncology.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Non-small-cell lung cancer (NSCLC) is a leading cause of cancer mortality globally.
- Liquid biopsy, utilizing circulating tumor cells (CTCs), offers a minimally invasive approach for cancer molecular profiling.
- Single-cell and next-generation sequencing (NGS) technologies enable detailed analysis of CTCs.
Purpose of the Study:
- To identify somatic variants in individual CTCs from NSCLC patients via targeted NGS.
- To assess the potential of CTC single-cell genomics for NSCLC precision oncology.
Main Methods:
- Blood samples (7.5 mL) were collected from 20 NSCLC patients and 11 healthy smokers.
- CTCs were isolated using immunofluorescence, individually retrieved, and DNA extracted.
- Targeted NGS was performed on 23 CTCs and 13 white blood cells across seven patients to detect single-nucleotide variants (SNVs) and insertions/deletions (Indels) in 65 cancer-related genes.
Main Results:
- NSCLC patients exhibited significantly higher CTC counts compared to control smokers (p = 0.0132).
- A total of 644 somatic variants were identified across CTCs within patients, with up to 137 variants per patient.
- Mutations with oncogenic impact were found in key genes including NF1, PTCH1, TP53, SMARCB1, SMAD4, KRAS, and ERBB2.
Conclusions:
- Single CTC-targeted NGS effectively detects heterogeneous and shared mutational signatures in NSCLC.
- CTC single-cell genomics holds significant potential for integration into NSCLC precision oncology strategies.
- This approach can provide valuable insights into tumor heterogeneity and guide personalized treatment decisions.
