Targeted Sequencing of Circulating Cell Free DNA Can Be Used to Monitor Therapeutic Efficacy of Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer Patients.
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Biomarkers, Tumor
/ genetics
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Circulating Tumor DNA
/ analysis
Disease Progression
ErbB Receptors
/ antagonists & inhibitors
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
High-Throughput Nucleotide Sequencing
Humans
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Mutation
Prognosis
Protein Kinase Inhibitors
/ therapeutic use
Tumor Burden
Tumor Cells, Cultured
Circulating tumor DNA
EGFR mutation
monitoring markers
non-small cell lung cancer
Journal
Cancer genomics & proteomics
ISSN: 1790-6245
Titre abrégé: Cancer Genomics Proteomics
Pays: Greece
ID NLM: 101188791
Informations de publication
Date de publication:
Historique:
received:
25
02
2020
revised:
13
03
2020
accepted:
14
03
2020
entrez:
25
6
2020
pubmed:
25
6
2020
medline:
12
2
2021
Statut:
ppublish
Résumé
Circulating tumor DNA (ctDNA) bears specific mutations derived from tumor cells. The amount of mutant ctDNA may reflect tumor burden. In this study, we detected epidermal growth factor receptor (EGFR) mutations in ctDNA as a monitoring marker for the response of non-small cell lung cancer (NSCLC) patients to tyrosine kinase inhibitors (TKIs). Serial plasma samples from eight NSCLC patients during TKI treatment were collected. Libraries with barcoded adapters were constructed from ctDNA of these plasma samples using a PCR-based targeted DNA panel. The libraries were then sequenced for measuring EGFR mutations. In addition, carcinoembryonic antigen (CEA) was also measured in these patients. In six patients who suffered disease progression (PD), five had elevated EGFR mutation reads before PD. In the two patients who did not develop PD, EGFR mutations remained undetectable in their plasma. The CEA levels were higher than the cutoff value in most samples and had a poor correlation with disease status. The mutation count of tumor-specific mutations can be a monitoring marker of TKI treatment in NSCLC patients.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Circulating tumor DNA (ctDNA) bears specific mutations derived from tumor cells. The amount of mutant ctDNA may reflect tumor burden. In this study, we detected epidermal growth factor receptor (EGFR) mutations in ctDNA as a monitoring marker for the response of non-small cell lung cancer (NSCLC) patients to tyrosine kinase inhibitors (TKIs).
PATIENTS AND METHODS
METHODS
Serial plasma samples from eight NSCLC patients during TKI treatment were collected. Libraries with barcoded adapters were constructed from ctDNA of these plasma samples using a PCR-based targeted DNA panel. The libraries were then sequenced for measuring EGFR mutations. In addition, carcinoembryonic antigen (CEA) was also measured in these patients.
RESULTS
RESULTS
In six patients who suffered disease progression (PD), five had elevated EGFR mutation reads before PD. In the two patients who did not develop PD, EGFR mutations remained undetectable in their plasma. The CEA levels were higher than the cutoff value in most samples and had a poor correlation with disease status.
CONCLUSION
CONCLUSIONS
The mutation count of tumor-specific mutations can be a monitoring marker of TKI treatment in NSCLC patients.
Identifiants
pubmed: 32576586
pii: 17/4/417
doi: 10.21873/cgp.20200
pmc: PMC7367604
doi:
Substances chimiques
Biomarkers, Tumor
0
Circulating Tumor DNA
0
Protein Kinase Inhibitors
0
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
417-423Informations de copyright
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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