Non-invasive detection of actionable mutations in advanced non-small-cell lung cancer using targeted sequencing of circulating tumor DNA

Wey Cheng Sim, Chet Hong Loh, Grace Li Xian Toh, Chia Wei Lim, Akhil Chopra, Alex Yuan Chi Chang, Liuh Ling Goh

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To evaluate the feasibility of detecting actionable gene mutations in circulating tumor DNA (ctDNA) in patients with advanced non-small-cell lung cancer (NSCLC) using targeted next-generation sequencing (NGS). Materials and methods: In total 50 plasma samples from patients newly diagnosed with advanced NSCLC or resistant to first-line tyrosine kinase inhibitors (TKIs) were subjected to deep sequencing on a seven-gene panel (BRAF, EGFR, ERBB2, KRAS, NRAS, PIK3CA, PTEN) incorporated with molecular barcodes to improve accuracy in variant detection. When possible, results were compared with those from matched tissue samples. Results: At least one alteration in the ctDNA was detected in 44 out of 50 patients (88%); EGFR was the most frequently mutated gene. Half the total number of patients (50%, 25 of 50) had at least one actionable genetic alteration with targeted therapies available for treatment. Our results showed a high concordance rate of 81% in detection of EGFR mutation between 26 matched tissue and plasma samples. For progressive patients, from whom tissue is mostly unavailable, the resistant EGFR T790 M mutation was validated using the droplet digital polymerase chain reaction (ddPCR), yielding a concordance of 92% between alternative platforms. Conclusion: Our study demonstrated that therapeutically actionable mutations can be detected with high accuracy in ctDNA using NGS. This promising approach offers alternative and non-invasive diagnostic methods for treatment guidance and clinical monitoring.

Original languageEnglish (US)
Pages (from-to)154-159
Number of pages6
JournalLung Cancer
Volume124
DOIs
StatePublished - Oct 2018
Externally publishedYes

Keywords

  • Actionable mutations
  • Circulating tumor DNA
  • Molecular barcode
  • Non-invasive
  • Non-small-cell lung cancer
  • Targeted sequencing

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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