Concordance of changes in the extracellular DNA of blood plasma and DNA of tumor tissue using the example of EGFR gene mutations in patients with non-small cell lung cancer

Gneusheva A.A.

Department of Theoretical Biochemistry with a Course in Clinical Biochemistry, Volgograd State Medical University of the Ministry of Health of Russian Federation, Volgograd, Russia

Verovsky V.E.

FSBEI HE «Volgograd state medical university», Volgograd, Russia

Zykova E.V.

Department of Theoretical Biochemistry with a Course in Clinical Biochemistry, Volgograd State Medical University of the Ministry of Health of Russian Federation, Volgograd, Russia

Ostrovskij O.V.

VolgGMU, Volgograd, Rossija

Concordance of changes in the extracellular DNA of blood plasma and DNA of tumor tissue using the example of EGFR gene mutations in patients with non-small cell lung cancer

Authors:

Gneusheva A.A., Verovsky V.E., Zykova E.V., Ostrovskij O.V.

More about the authors

Journal: Laboratory Service. 2018;7(4): 19‑25

DOI: 10.17116/labs2018704119

Downloaded: 8

Download PDF (RU)

Contact the author

Table of contents

To cite this article:

Gneusheva AA, Verovsky VE, Zykova EV, Ostrovskij OV. Concordance of changes in the extracellular DNA of blood plasma and DNA of tumor tissue using the example of EGFR gene mutations in patients with non-small cell lung cancer. Laboratory Service. 2018;7(4):19‑25. (In Russ.)
https://doi.org/10.17116/labs2018704119

Close metadata

Recommended articles:

Comparative analysis of EGFR gene mutations (exon 20) in sinonasal papillomas of inverted and oncocytic types. Russian Journal of Archive of Pathology. 2025;(1):16-21

The presence of mutations found in both extracellular DNA (cfDNA) and tumor tissue can serve as evidence of the tumor origin of the cfDNA. The aim of this study was to determine the mutational status of cfDNA in plasma and to compare that with the mutational changes in DNA of the tumor to identify possible sources and origin of the cfDNA. Material and methods. The methodology for conducting the metaanalysis is carried out in accordance with the provisions of «Preferred reporting parameters for systematic reviews and metaanalysis (PRISMA)». In accordance with the inclusion criteria, 28 studies involving 3371 people were combined to perform the meta-analysis, in which the comparison of the mutational status of the EGFR gene in the cfDNA of plasma and tumor tissue was carried out. In a laboratory study, 13 patients with a diagnosis of non-small cell lung cancer adenocarcinoma (76.9%) and squamous cell carcinoma were evaluated. Results. Metaanalysis showed that there was no heterogeneity between studies (Q=0.001699, I2=0), the average percentage of concordance of the mutational status of the tumor DNA and the cfDNA in blood was 88.1% (95% CI 86.96—89.18%). In the study of genetic changes in tumor samples and cfDNA in plasma from patients with non-small cell lung cancer, it was shown that the activating mutation in the EGFR gene in our sample was present in 2 patients. Also, the same mutation was detected in plasma cfDNA in 50% of samples from these patients. The remaining patients had no mutation in either the tumor samples or in the plasma cfDNA. Therefore, the percentage of concordance of the mutational status of the tumor and the cfDNA of the blood (concordance) was 92.3% (95% CI 63.9—99.8%). Conclusions. It can be concluded that the results of this study may indicate a possible tumor origin of the cfDNA, which opens up new possibilities for understanding the biological role of the cfDNA in plasma.

Keywords:

cell free DNA

non-small lung cancer

EGFR

Authors:

Gneusheva A.A.

Department of Theoretical Biochemistry with a Course in Clinical Biochemistry, Volgograd State Medical University of the Ministry of Health of Russian Federation, Volgograd, Russia

Verovsky V.E.

FSBEI HE «Volgograd state medical university», Volgograd, Russia

Zykova E.V.

Department of Theoretical Biochemistry with a Course in Clinical Biochemistry, Volgograd State Medical University of the Ministry of Health of Russian Federation, Volgograd, Russia

Ostrovskij O.V.

VolgGMU, Volgograd, Rossija

List of references:

Kushlinskij NE, Krasil’nikova MA. Biologicheskie markery opuholej: fundamental’nye klinicheskie issledovaniya. M.: Izdatel’stvo RAMN, 2017:632. (In Russ.)
Diehl F, Li M, Dressman D, He Y, Shen D, Szabo S, et al. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci USA. 2005 Nov 8;102(45):16368-16373.
Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004 Mar 5;303(5663):1532-1535.
Erpenbeck L, SchÃ¶n MP. Neutrophil extracellular traps: protagonists of cancer progression? Oncogene. 2017 May 4;36(18):2483-2490.
Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions 4.2.6 [updated September 2006]. http://www.cochrane.org/resources/handbook/hbook.htm (accessed 6th October 2006)
Veldore VH, Choughule A, Routhu T, Mandloi N, Noronha V, Joshi A, Dutt A, Gupta R, Vedam R, Prabhash K. Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non-small cell lung cancer. Lung Cancer (Auckl). 2018;3:9:1-11.
MÃ¶hrmann L, Huang HJ, Hong DS, Tsimberidou AM, Fu S, Piha-Paul SA, Subbiah V, Karp DD. Liquid biopsies using plasma exosomal nucleic acids and plasma cell-free DNA compared with clinical outcomes of patients with advanced cancers. Clinical Cancer Research. 2018;24(1);181-188.
Sung JS, Chong HY, Kwon NJ, Kim HM, Lee JW, Kim B, LeeÂ SB, Park CW, Choi JY, Chang WJ, Choi YJ, Lee SY, Kang EJ, Park KH, Kim YH. Detection of somatic variants and EGFR mutations in cell-free DNA from non-small cell lung cancer patients by ultra-deep sequencing using the ion ampliseq cancer hotspot panel and droplet digital polymerase chain reaction. Oncotarget. 2017;15:8(63):106901-106912.
Yu Q, Huang F, Zhang M, Ji H, Wu S, Zhao Y, Zhang C, Wu J, Wang B, Pan B, Zhang X, Guo W. Multiplex picoliter-droplet digiÂtal PCR for quantitative assessment of EGFR mutations in circulating cell-free DNA derived from advanced non-small cell lung cancer patients. Mol Med Rep. 2017;2:1157-1166.
Fassunke J, Ihle MA, Lenze D, Lehmann A, Hummel M, Vollbrecht C, Penzel R, Volckmar AL, Stenzinger A, Endris V, Jung A, Lehmann U, Zeugner S, Baretton G, Kreipe H, Schirmacher P, Kirchner T, Dietel M, Büttner R, Merkelbach-Bruse S. EGFR T790M mutation testing of non-small cell lung cancer tissue and blood samples artificially spiked with circulating cell-free tumor DNA: results of a round robin trial. Virchows Arch. 2017;(4):509-520. https://doi.org/10.1007/s00428-017-2226-8
Li Y, Xu H, Su S, Ye J, Chen J, Jin X, Lin Q, Zhang D, Ye C, Chen C. Clinical validation of a highly sensitive assay to detect EGFR mutations in plasma cell-free DNAfrom patients with advanced lung adenocarcinoma. PLoS One. 2017 Aug 22;12(8).
Bartels S, Persing S, Hasemeier B, Schipper E, Kreipe H, Lehmann U. Molecular analysis of circulating cell-free DNA from lung cancer patients in Routine Laboratory Practice: a cross-platform comparison of three different molecular methods for mutation detection. J Mol Diagn. 2017;19(5):722-732.
Ni J, Weng L, Liu Y, Sun Z, Bai C, Wang Y. Dynamic monitoring of EGFR mutations in circulating cell-free DNA for EGFR-mutant metastatic patients with lung cancer: Early detection of drug resistance and prognostic significance. Oncol Lett. 2017;13:4549-4557.
Zhu YJ. Association of mutant EGFR L858R and exon 19 concentration in circulating cell-free DNA using droplet digital PCR with response to EGFR-TKIs in NSCLC. Oncol Lett. 2017;14:2573-2579.
Yang Y, Shen X, Li R, Shen J, Zhang H, Yu L, Liu B, Wang L. The detection and significance of EGFR and BRAF in cell-free DNA of peripheral blood in NSCLC. Oncotarget. 2017;8(30):49773-49782.
Wan R, Wang Z, Lee JJ, Wang S, Li Q, Tang F, Wang J, Sun Y, Bai H, Wang D, Zhao J, Duan J, Zhuo M, An T, Wu M, Chen Z, Yang Z, Wang J. Comprehensive analysis of the discordance of EGFR mutation status between tumor tissues and matched circulating tumor DNA in advanced non-small cell lung cancer. J Thorac Oncol. 2017;12(9):1376-1387.
Zhang C, Wei B, Li P, Yang K, Wang Z, Ma J, Guo Y. Prognostic value of plasma EGFR ctDNA in NSCLC patients treated with EGFR-TKIs. PLoS One. 2017;12(3):e0173524.
Imamura F, Uchida J, Kukita Y, Kumagai T, Nishino K, InoueÂ T, Kimura M. Early responses of EGFR circulating tumor DNA to EGFR tyrosine kinase inhibitors in lung cancer treatment. Oncotarget. 2016;7(44):71782-71789.
Villaflor V, Won B, Nagy R, Banks K, Lanman RB, Talasaz A, Salgia R. Biopsy-free circulating tumor DNA assay identifies actionable mutations in lung cancer. Oncotarget. 2016;11:7(41):66880-66891.
Nakahara Y, Takagi Y, Hosomi Y, Kagei A, Yamamoto T, SawadaÂ T, Yomota M, Okuma Y, Mikura S, Okamura T. Noninvasive monitoring of the genetic evolution of EGFR-mutant non-small-cell lung cancer by analyzing circulating tumor DNA during combination chemotherapy with gefitinib and pemetrexed or S-1. Onco Targets Ther. 2016;9:5287-5295.
Chae YK, Davis AA, Carneiro BA, Chandra S, Mohindra N, Kalyan A, Kaplan J, Matsangou M, Pai S, Costa R, JovanovicÂ B, Cristofanilli M, Platanias LC, Giles FJ. Concordance between genomic alterations assessed by next-generation sequencing in tumor tissue or circulating cell-free DNA. Oncotarget. 2016;4:7(40):65364-65373.
Reck M, Hagiwara K, Han B, Tjulandin S, Grohé C, Yokoi T, Morabito A, Novello S’Arriola E, Molinier O, McCormack R, Ratcliffe M, Normanno N. ctDNA determination of EGFR mutation status in European and Japanese patients with advanced NSCLC. The ASSESS Study. J Thorac Oncol. 2016;11:1682-1689.
Rachiglio AM, Esposito Abate R, Sacco A, Pasquale R, Fenizia F, Lambiase M, Morabito A, Montanino A, Rocco G, Romano C, Nappi A, Iaffaioli R, Tatangelo F, Botti G, Ciardiello F, MaielloÂ M, De Luca A, Normanno N. Limits and potential of targeted sequencing analysis of liquid biopsy in patients with lung and colon carcinoma. Oncotarget. 2016;11:7(41):66595-66605.
Ma M, Shi C, Qian J, Teng J, Zhong H, Han B. Comparison of plasma and tissue samples in epidermal growth factor receptor mutation by ARMS in advanced non-small cell lung cancer. Gene. 2016 Oct 10;591(1):58-64.
Oxnard GR, Thress KS, Alden RS, Lawrance R, Paweletz CP, Cantarini M, Yang JC, Barrett JC, Jänne PA. Association between plasma genotyping and outcomes of treatment with osimertinib (AZD9291) in advanced non-small-cell lung cancer. J Clin Oncol. 2016;34(28).
Duan H, Lu J, Lu T, Gao J, Zhang J, Xu Y, Wang M, Wu H, LiangÂ Z, Liu T. Comparison of EGFR mutation status between plasma and tumor tissue in non-small cell lung cancer using the Scorpion ARMS method and the possible prognostic significance of plasma EGFR mutation status. Int J Clin Exp Pathol. 2015;1:8(10):13136-13145.
Ishii H, Azuma K, Sakai K, Kawahara A, Yamada K, Tokito T, Okamoto I, Nishio K, Hoshino T. Digital PCR analysis of plasma cell-free DNA for non-invasive detection of drug resistance meÂchanisms in EGFR mutant NSCLC: Correlation with paired tumor samples. Oncotarget. 2015;6(31):30850-30858.
Taniguchi K, Uchida J, Nishino K, Kumagai T, Okuyama T, OkamiÂ J, Higashiyama M, Kodama K, Imamura F, Kato K. Quantitative detection of EGFR mutations in circulating tumor DNA derived from lung adenocarcinomas. Clinical Cancer Research. 2011.
Sriram KB, Tan ME, Savarimuthu SM, Wright CM, Relan V, Stockwell RE, Clarke BE, Duhig EE, Yang IA. Screning for activating EGFR mutations in surgically resected nonsmall cell lung cancer. Eur Respir. 2011;38:903-910.
Kumar SR, Singh GV, Bharti AC, Mohan A, Das BC. Plasma DNA level in predicting therapeutic efficacy in advanced non-small cell lung cancer. Eur Respir. 2010;4885-892.
Kuang Y, Rogers A, Yeap BY, Wang L, Makrigiorgos M, Vetrand K, Thiede S, Distel RJ, Jaänne PA. Noninvasive detection of EGFR T790M in gefitinib or erlotinib resistant non-small cell lung cancer. Clin Cancer Res. 2009 Apr 15;15(8):2630-2636.
Tony KF, Yung KC, Chan A, Tony SK, Mok, et al. Single-molecule detection of epidermal growth factor receptor mutations in plasma by microfluidics digital PCR in non-small cell lung cancer patient. Clin Cancer Res. 2009;15:2076-2084.
Kimura H, Suminoe M, Kasahara K, Sone T, Araya T, Tamori S, Koizumi F, Nishio K, Miyamoto K, Fujimura M, Nakao S. Evaluation of epidermal growth factor receptor mutation status in serum DNA as a predictor of response to gefitinib (IRESSA). Br J Cancer. 2007 Sep 11;97(6):778-784

Close metadata