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

https://doi.org/10.21294/1814-4861-2018-17-5-52-59

Abstract

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.

About the Authors

V. A. Shamanin
Federal Research Center of Fundamental and Translational Medicine; Biolink Ltd
Russian Federation

Vladimir A. Shamanin, PhD, Senior Researcher, Federal Research Center for Fundamental and Translational Medicine

2, Timakova Street, 630117-Novosibirsk



I. V. Karpov
Federal Research Center of Fundamental and Translational Medicine; Biolink Ltd
Russian Federation

Igor V. Karpov, Laboratory assistant, Federal Research Center for Fundamental and Translational Medicine

2, Timakova Street, 630117-Novosibirsk



P. А. Gervas
Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences
Russian Federation

Polina A. Gervas, PhD, Research Fellow

5, Kooperativny Street, 634009-Tomsk



N. V. Cherdyntseva
Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences
Russian Federation

Nadezhda V. Cherdyntseva, DSc, Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Laboratory of Molecular Oncology and Immunology

5, Kooperativny Street, 634009-Tomsk

ResearcherID (WOS): C-7943-2012. Author ID (Scopus): 6603911744



E. I. Simolina
Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences
Russian Federation

Elena I. Simolina, MD, PhD, Researcher, Department of Chemotherapy

5, Kooperativny Street, 634009-Tomsk



V. V. Kozlov
Novosibirsk Regional Oncology Clinic
Russian Federation

Vadim V. Kozlov, MD, PhD, Head of Oncology Department № 3

2, Plahotnogo Street, 630108-Novosibirsk



S. P. Kovalenko
Federal Research Center of Fundamental and Translational Medicine; Biolink Ltd
Russian Federation

Sergey P. Kovalenko, DSc, Head of Laboratory, Federal Research Center for Fundamental and Translational Medicine

2, Timakova Street, 630117-Novosibirsk



References

1. Morgensztern D., Campo M.J., Dahlberg S.E., Doebele R.C., Garon E., Gerber D.E., Goldberg S.B., Hammerman P.S., Heist R.S., Hensing T., Horn L., Ramalingam S.S., Rudin C.M., Salgia R., Sequist L.V., Shaw A.T., Simon G.R., Somaiah N., Spigel D.R., Wrangle J., Johnson D., Herbst R.S., Bunn P., Govindan R. Molecularly targeted therapies in nonsmallcell lung cancer annual update 2014. J Thorac Oncol. 2015 Jan; 10 (1 Suppl 1): S1–63. doi: 10.1097/JTO.0000000000000405.

2. Soria J.C., Ohe Y., Vansteenkiste J., Reungwetwattana T., Chewaskulyong B., Lee K.H., Dechaphunkul A., Imamura F., Nogami N., Kurata T., Okamoto I., Zhou C., Cho B.C., Cheng Y., Cho E.K., Voon P.J., Planchard D., Su W.C., Gray J.E., Lee S.M., Hodge R., Marotti M., Rukazenkov Y., Ramalingam S.S.; FLAURA Investigators. Osimertinib in Untreated EGFRMutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Jan 11; 378 (2): 113–125. doi: 10.1056/NEJMoa1713137.

3. Kerr K.M., Bubendorf L., Edelman M.J., Marchetti A., Mok T., Novello S., O’Byrne K., Stahel R., Peters S., Felip E.; Panel Members; Panel Members. Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non-small-cell lung cancer. Ann Oncol. 2014 Sep; 25 (9): 1681–90. doi: 10.1093/annonc/mdu145.

4. Kalemkerian G.P., Narula N., Kennedy E.B., Biermann W.A., Donington J., Leighl N.B., Lew M., Pantelas J., Ramalingam S.S., Reck M., Saqi A., Simoff M., Singh N., Sundaram B. Molecular Testing Guideline for the Selection of Patients With Lung Cancer for Treatment With Targeted Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update. J Clin Oncol. 2018 Mar 20; 36 (9): 911–919. doi: 10.1200/JCO.2017.76.7293.

5. Rolfo C., Mack P.C., Scagliotti G.V., Baas P., Barlesi F., Bivona T.G., Herbst R.S., Mok T.S., Peled N., Pirker R., Raez L.E., Reck M., Riess J.W., Sequist L.V., Shepherd F.A., Sholl L.M., Tan D.S., Wakelee H.A., Wistuba I.I., Wynes M.W., Carbone D.P., Hirsch F.R., Gandara D.R. IASLC Statement Paper: Liquid Biopsy for Advanced Non-Small Cell Lung Cancer (NSCLC). J Thorac Oncol. 2018 Sep; 13 (9): 1248–1268. doi: 10.1016/j.jtho.2018.05.030.

6. Francis G., Stein S. Circulating Cell-Free Tumour DNA in the Management of Cancer. Int J Mol Sci. 2015 Jun 19; 16(6): 14122–42. doi: 10.3390/ijms160614122.

7. Wu Y.L., Sequist L.V., Hu C.P., Feng J., Lu S., Huang Y., Li W., Hou M., Schuler M., Mok T., Yamamoto N., O’Byrne K., Hirsh V., Gibson N., Massey D., Kim M., Yang J.C. EGFR mutation detection in circulating cellfree DNA of lung adenocarcinoma patients: analysis of LUX-Lung 3 and 6. Br J Cancer. 2017 Jan 17; 116 (2): 175–185. doi: 10.1038/bjc.2016.420.


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For citations:


Shamanin V.A., Karpov I.V., Gervas P.А., Cherdyntseva N.V., Simolina E.I., Kozlov V.V., Kovalenko S.P. MONITORING OF EGFR MUTATIONS IN THE CIRCULATING TUMOR DNA FROM BLOOD PLASMA OF PATIENTS WITH NON-SMALL CELL LUNG CANCER. Siberian journal of oncology. 2018;17(5):52-59. https://doi.org/10.21294/1814-4861-2018-17-5-52-59

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ISSN 1814-4861 (Print)
ISSN 2312-3168 (Online)