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.
Acrylamides
/ pharmacology
Alleles
Amino Acid Substitution
Aniline Compounds
/ pharmacology
Antineoplastic Agents
/ pharmacology
Biomarkers, Tumor
Child, Preschool
ErbB Receptors
/ genetics
Female
Genotype
High-Throughput Nucleotide Sequencing
Humans
Infant
Liquid Biopsy
Lung Neoplasms
/ drug therapy
Male
Mutation
Protein Kinase Inhibitors
/ pharmacology
Real-Time Polymerase Chain Reaction
Circulating tumor DNA
droplet digital PCR
next generation sequencing
plasma genotyping
resistance mechanisms
Journal
Thoracic cancer
ISSN: 1759-7714
Titre abrégé: Thorac Cancer
Pays: Singapore
ID NLM: 101531441
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
12
06
2019
revised:
04
07
2019
accepted:
05
07
2019
pubmed:
16
8
2019
medline:
28
7
2020
entrez:
16
8
2019
Statut:
ppublish
Résumé
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. 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. High concordance of allelic fractions were seen in matched plasma NGS and ddPCR for activating EGFR mutations and T790M mutations (R 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.
Sections du résumé
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.
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.
RESULTS
High concordance of allelic fractions were seen in matched plasma NGS and ddPCR for activating EGFR mutations and T790M mutations (R
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.
Identifiants
pubmed: 31414729
doi: 10.1111/1759-7714.13154
pmc: PMC6775001
doi:
Substances chimiques
Acrylamides
0
Aniline Compounds
0
Antineoplastic Agents
0
Biomarkers, Tumor
0
Protein Kinase Inhibitors
0
osimertinib
3C06JJ0Z2O
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1879-1884Informations de copyright
© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
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