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Plasma next generation sequencing and droplet digital PCR-based detection of epidermal growth factor receptor (EGFR) mutations in patients with advanced lung cancer treated with subsequent-line osimertinib.
- Source :
-
Thoracic cancer [Thorac Cancer] 2019 Oct; Vol. 10 (10), pp. 1879-1884. Date of Electronic Publication: 2019 Aug 15. - Publication Year :
- 2019
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Abstract
- Background: Gene mutation analysis from plasma circulating tumor DNA (ctDNA) can provide timely information regarding the mechanism of resistance that could translate to personalised treatment. We compared concordance rate of next generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR) in the detection of the EGFR activating and T790M mutation from plasma ctDNA with diagnostic tissue biopsy-based assays. The second objective was to test whether putative osimertinib resistance associated mutations were detectable from plasma using NGS.<br />Methods: From January 2016 to December 2017, we prospectively collected plasma samples from patients prior to commencement of second- or third-line osimertinib therapy and upon disease progression, in a single tertiary hospital in South Western Sydney, Australia. Amplicon-based NGS and ddPCR assays were used to detect activating epidermal growth factor receptor (EGFR) and T790M mutations in 18 plasma samples from nine patients; all patients were required to have tissue biopsies with known EGFR status.<br />Results: High concordance of allelic fractions were seen in matched plasma NGS and ddPCR for activating EGFR mutations and T790M mutations (R <superscript>2</superscript> = 0.92, Pā<ā0.0001). Using tissue biopsies as reference standard, sensitivity was 100% for NGS and 94% for ddPCR. Several possible osimertinib resistance associated mutations, including PIK3CA, BRAF and TP53 mutations, were detected by NGS in samples upon progression on osimertinib therapy.<br />Conclusion: ddPCR assays for EGFR mutations appear to be as sensitive and highly concordant as amplicon-based NGS. NGS has the ability to detect novel resistance mutations.<br /> (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)
- Subjects :
- Acrylamides pharmacology
Acrylamides therapeutic use
Alleles
Amino Acid Substitution
Aniline Compounds pharmacology
Aniline Compounds therapeutic use
Antineoplastic Agents pharmacology
Antineoplastic Agents therapeutic use
Biomarkers, Tumor
Child, Preschool
ErbB Receptors genetics
Female
Genotype
High-Throughput Nucleotide Sequencing
Humans
Infant
Liquid Biopsy
Lung Neoplasms drug therapy
Lung Neoplasms pathology
Male
Protein Kinase Inhibitors pharmacology
Protein Kinase Inhibitors therapeutic use
Real-Time Polymerase Chain Reaction
Lung Neoplasms genetics
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1759-7714
- Volume :
- 10
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Thoracic cancer
- Publication Type :
- Academic Journal
- Accession number :
- 31414729
- Full Text :
- https://doi.org/10.1111/1759-7714.13154