MONITORING OF EGFR MUTATIONS IN THE CIRCULATING TUMOR DNA FROM BLOOD PLASMA OF PATIENTS WITH NON-SMALL CELL LUNG CANCER

Activating mutations of EGFR are associated with sensitivity of non-small cell lung cancer (NSCLC ) to tyrosine kinase inhibitors (TKI). Liquid biopsy using circulating cell-free tumor DNA (cfDNA) is proposed in cases when formalin fixed paraffin embedded (FFPE) tumor tissue is not available and for...

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Main Authors: V. A. Shamanin, I. V. Karpov, P. А. Gervas, N. V. Cherdyntseva, E. I. Simolina, V. V. Kozlov, S. P. Kovalenko
Format: Article
Language:Russian
Published: Russian Academy of Sciences, Tomsk National Research Medical Center 2018-11-01
Series:Сибирский онкологический журнал
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Online Access:https://www.siboncoj.ru/jour/article/view/858
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author V. A. Shamanin
I. V. Karpov
P. А. Gervas
N. V. Cherdyntseva
E. I. Simolina
V. V. Kozlov
S. P. Kovalenko
author_facet V. A. Shamanin
I. V. Karpov
P. А. Gervas
N. V. Cherdyntseva
E. I. Simolina
V. V. Kozlov
S. P. Kovalenko
author_sort V. A. Shamanin
collection DOAJ
description Activating mutations of EGFR are associated with sensitivity of non-small cell lung cancer (NSCLC ) to tyrosine kinase inhibitors (TKI). Liquid biopsy using circulating cell-free tumor DNA (cfDNA) is proposed in cases when formalin fixed paraffin embedded (FFPE) tumor tissue is not available and for monitoring of EGFR status. In the study we evaluated new qPC R assay for EGFR mutations in plasma cfDNA. Sensitivity of the assay was 1 % of the mutant allele for L858R, L861Q, S768I mutations and deletions in exon 19, and 5 % of the mutant allele for G719X or T790M mutations Before surgery, mutation was detected in plasma of 4 out of 7 patients (57 %) with mutant EGFR in FFPE tumor tissue. Mutations found in cfDNA completely matched those found in tumor tissue in 2 cases. In one case with G719X and S768I mutations in FFPE tissue, only S768I was found in cfDNA. In another case, T790M was detected in plasma in addition to L858R that was present in tumor tissue. No EGFR mutations were detected in plasma DNA from 12 healthy volunteers and 13 cases of NSCLC with wt EGFR suggesting 100 % specificity of the assay. Liquid biopsy detected EGFR mutations in cfDNA in 8 of 16 cases of NSCLC with mutant EGFR being under therapy with TKI. Among them, 7 cases had mutations in liquid biopsy that matched those in tumor tissue and another case had T790M in addition to L858R. In 3 cases increased mutant allele frequency was detected 212 months before clinical progression.
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spelling doaj-art-94c29e7e4b5a4b60917e541cd444965c2025-08-20T03:56:24ZrusRussian Academy of Sciences, Tomsk National Research Medical CenterСибирский онкологический журнал1814-48612312-31682018-11-01175525910.21294/1814-4861-2018-17-5-52-59576MONITORING OF EGFR MUTATIONS IN THE CIRCULATING TUMOR DNA FROM BLOOD PLASMA OF PATIENTS WITH NON-SMALL CELL LUNG CANCERV. A. Shamanin0I. V. Karpov1P. А. Gervas2N. V. Cherdyntseva3E. I. Simolina4V. V. Kozlov5S. P. Kovalenko6Federal Research Center of Fundamental and Translational Medicine; Biolink LtdFederal Research Center of Fundamental and Translational Medicine; Biolink LtdCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesNovosibirsk Regional Oncology ClinicFederal Research Center of Fundamental and Translational Medicine; Biolink LtdActivating mutations of EGFR are associated with sensitivity of non-small cell lung cancer (NSCLC ) to tyrosine kinase inhibitors (TKI). Liquid biopsy using circulating cell-free tumor DNA (cfDNA) is proposed in cases when formalin fixed paraffin embedded (FFPE) tumor tissue is not available and for monitoring of EGFR status. In the study we evaluated new qPC R assay for EGFR mutations in plasma cfDNA. Sensitivity of the assay was 1 % of the mutant allele for L858R, L861Q, S768I mutations and deletions in exon 19, and 5 % of the mutant allele for G719X or T790M mutations Before surgery, mutation was detected in plasma of 4 out of 7 patients (57 %) with mutant EGFR in FFPE tumor tissue. Mutations found in cfDNA completely matched those found in tumor tissue in 2 cases. In one case with G719X and S768I mutations in FFPE tissue, only S768I was found in cfDNA. In another case, T790M was detected in plasma in addition to L858R that was present in tumor tissue. No EGFR mutations were detected in plasma DNA from 12 healthy volunteers and 13 cases of NSCLC with wt EGFR suggesting 100 % specificity of the assay. Liquid biopsy detected EGFR mutations in cfDNA in 8 of 16 cases of NSCLC with mutant EGFR being under therapy with TKI. Among them, 7 cases had mutations in liquid biopsy that matched those in tumor tissue and another case had T790M in addition to L858R. In 3 cases increased mutant allele frequency was detected 212 months before clinical progression.https://www.siboncoj.ru/jour/article/view/858liquid biopsyqpcregfrmutationlung cancer
spellingShingle V. A. Shamanin
I. V. Karpov
P. А. Gervas
N. V. Cherdyntseva
E. I. Simolina
V. V. Kozlov
S. P. Kovalenko
MONITORING OF EGFR MUTATIONS IN THE CIRCULATING TUMOR DNA FROM BLOOD PLASMA OF PATIENTS WITH NON-SMALL CELL LUNG CANCER
Сибирский онкологический журнал
liquid biopsy
qpcr
egfr
mutation
lung cancer
title MONITORING OF EGFR MUTATIONS IN THE CIRCULATING TUMOR DNA FROM BLOOD PLASMA OF PATIENTS WITH NON-SMALL CELL LUNG CANCER
title_full MONITORING OF EGFR MUTATIONS IN THE CIRCULATING TUMOR DNA FROM BLOOD PLASMA OF PATIENTS WITH NON-SMALL CELL LUNG CANCER
title_fullStr MONITORING OF EGFR MUTATIONS IN THE CIRCULATING TUMOR DNA FROM BLOOD PLASMA OF PATIENTS WITH NON-SMALL CELL LUNG CANCER
title_full_unstemmed MONITORING OF EGFR MUTATIONS IN THE CIRCULATING TUMOR DNA FROM BLOOD PLASMA OF PATIENTS WITH NON-SMALL CELL LUNG CANCER
title_short MONITORING OF EGFR MUTATIONS IN THE CIRCULATING TUMOR DNA FROM BLOOD PLASMA OF PATIENTS WITH NON-SMALL CELL LUNG CANCER
title_sort monitoring of egfr mutations in the circulating tumor dna from blood plasma of patients with non small cell lung cancer
topic liquid biopsy
qpcr
egfr
mutation
lung cancer
url https://www.siboncoj.ru/jour/article/view/858
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