https://doi.org/10.4081/monaldi.2022.2280
Detection of clinically-relevant EGFR variations in de novo small cell lung carcinoma by droplet digital PCR
Submitted: March 29, 2022
Accepted: August 2, 2022
Published: September 2, 2022
Accepted: August 2, 2022
Abstract Views: 1000
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Targeted therapy that utilizes tyrosine kinase inhibitors (TKIs), specific to epidermal growth factor receptors (EGFR) has changed the landscape of treatment of non-small cell lung cancer (NSCLC). The success or failure of this approach depends on presence of certain variations in the tyrosine kinase domain of EGFR gene. Generally, patients diagnosed with Small cell lung cancer (SCLC) are considered ineligible for TKI therapy owing to the absence of EGFR variations. . However, there is evidence of these variations being detected in SCLCs, both in de-novo and in transformed SCLCs (TKI-treated adenocarcinomas). Despite the presence of clinically-relevant EGFR variations in SCLCs, the response to TKIs has been inconsistent. Liquid biopsy is a well-established approach in lung cancer management with proven diagnostic, prognostic and predictive applications. It relies on detection of circulating tumor-derived nucleic acids present in plasma of the patient. In this study, a liquid biopsy approach was utilized to screen 118 consecutive lung cancer patients for four clinically-relevant variations in EGFR gene, which included three activating/sensitizing variations (Ex18 G719S, Ex19del E746-A750 and Ex21 L858R) and one acquired/resistance (Ex20 T790M, de novo) variation by droplet digital PCR, the most advanced third generation PCR technique. As expected, clinically-relevant EGFR variations were found in majority of the non-small cell lung cancer cases. However, among the handful of small cell lung cancer samples screened, sensitizing variations (Ex18 G719S and Ex21 L858R) were seen in almost all of them. Interestingly, Ex20 T790M variation was not detected in any of the cases screened. The results of our study indicate that EGFR variations are present in SCLCs and highly sensitive liquid biopsy techniques like ddPCR can be effectively utilized for this purpose of screening EGFR variations in such samples.
Franco F, Carcereny E, Guirado M, et al. Epidemiology, treatment, and survival in small cell lung cancer in Spain: Data from the Thoracic Tumor Registry. PLoS One 2021;16:e0251761.
DOI: https://doi.org/10.1371/journal.pone.0251761
Dómine M, Moran T, Isla D, et al. SEOM clinical guidelines for the treatment of small-cell lung cancer (SCLC) (2019). Clin Transl Oncol 2020;22:245–55.
DOI: https://doi.org/10.1007/s12094-020-02295-w
Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007;7:169-81.
DOI: https://doi.org/10.1038/nrc2088
Li K, Yang M, Liang N, Li S. Determining EGFR-TKI sensitivity of G719X and other uncommon EGFR mutations in nonsmall cell lung cancer: perplexity and solution (Review). Oncol Rep 2017;37:1347-58.
DOI: https://doi.org/10.3892/or.2017.5409
Varghese AM, Zakowski MF, Yu HA, et al. Small-cell lung cancers in patients who never smoked cigarettes. J Thorac Oncol 2014;9:892–6.
DOI: https://doi.org/10.1097/JTO.0000000000000142
Ferrer L, Giaj Levra M, Brevet M, et al. A brief report of transformation from NSCLC to SCLC: molecular and therapeutic characteristics. J Thorac Oncol 2019;14:130-4.
DOI: https://doi.org/10.1016/j.jtho.2018.08.2028
Marcoux N, Gettinger SN, O`Kane G, et al. EGFR-mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: clinical outcomes. J Clin Oncol 2018;37:278–85.
DOI: https://doi.org/10.1200/JCO.18.01585
Takagi Y, Nakahara Y, Hosomi Y, et al. Small-cell lung cancer with a rare epidermal growth factor receptor gene mutation showing “wax-and-wane” transformation. BMC Cancer 2013;13:529.
DOI: https://doi.org/10.1186/1471-2407-13-529
Tang H, Zhang J, Hu X, et al. Egfr mutations in small cell lung cancer (sclc): genetic heterogeneity and prognostic impact. J Thorac Oncol 2017;12:S710-1.
DOI: https://doi.org/10.1016/j.jtho.2016.11.936
Wang L, Dong F, Su J, et al. Resistance to both chemotherapy and egfr-tki in small cell lung cancer with egfr19-del mutation: a case report. Front Oncol 2020;10:1048.
DOI: https://doi.org/10.3389/fonc.2020.01048
Arjuna S, Venkataram R, Dechamma PN, et al. Non-invasive detection of EGFR mutations by cell free loop-mediated isothermal amplification (CF-LAMP). Sci Rep2020;10:17559.
DOI: https://doi.org/10.1038/s41598-020-74689-3
Arjuna S, Chakraborty G, Venkataram R, et al. Detection of epidermal growth factor receptor T790M mutation by allele-specific loop mediated isothermal amplification. J Carcinog 2020;19:3.
DOI: https://doi.org/10.4103/jcar.JCar_6_20
Crowley E, Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer- genetics in the blood. Nat Rev Clin Oncol 2013;10:472-84.
DOI: https://doi.org/10.1038/nrclinonc.2013.110
Santarpia M, Liguori A, D’Aveni A, et al. Liquid biopsy for lung cancer early detection. J Thorac Dis 2018;10:S882-97.
DOI: https://doi.org/10.21037/jtd.2018.03.81
Zhang R, Chen B, Tong X, et al. Diagnostic accuracy of droplet digital PCR for detection of EGFR T790M mutation in circulating tumor DNA. Cancer Manag Res 2018;10:1209-18.
DOI: https://doi.org/10.2147/CMAR.S161382
Watanabe M, Kawaguchi T, Isa S, et al. Ultra-sensitive detection of the pre-treatment EGFR T790M mutation in non-small cell lung cancer patients with an EGFR-activating mutation using droplet digital PCR. Clin Cancer Res 2015;21:3552-60.
DOI: https://doi.org/10.1158/1078-0432.CCR-14-2151
Zhang B, Xu C, Shao Y, et al. Comparison of droplet digital PCR and conventional quantitative PCR for measuring EGFR gene mutation. Exp Ther Med 2015;9:1383-8.
DOI: https://doi.org/10.3892/etm.2015.2221
Hindson B, Ness K, Masquelier D, et al. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal Chem 2011;83:8604-10.
DOI: https://doi.org/10.1021/ac202028g
Zhu G, Ye X, Dong Z, Lu Y, Sun Y, Liu Y, et al. Highly sensitive droplet digital pcr method for detection of egfr-activating mutations in plasma cell-free DNA from patients with advanced non-small cell lung cancer. J Mol Diagn 2015;17:265-72.
DOI: https://doi.org/10.1016/j.jmoldx.2015.01.004
Oxnard G, Paweletz C, Kuang Y, et al. Noninvasive detection of response and resistance in EGFR mutant lung cancer using quantitative next-generation genotyping of cell-free plasma DNA. Clin Cancer Res 2014;20:1698-705.
DOI: https://doi.org/10.1158/1078-0432.CCR-13-2482
Bordi P, Tiseo M, Barbieri F, et al. Gene mutations in small-cell lung cancer (SCLC): results of a panel of 6 genes in a cohort of Italian patients. Lung Cancer 2014;86:324–8.
DOI: https://doi.org/10.1016/j.lungcan.2014.10.002
Tatematsu A, Shimizu J, Murakami Y, et al. Epidermal growth factor receptor mutations in small cell lung cancer. Clin Cancer Res 2008;14:6092–6.
DOI: https://doi.org/10.1158/1078-0432.CCR-08-0332
Wang Z, Jiang Z, Lu H. Molecular genetic profiling of small cell lung carcinoma in a Chinese cohort. Transl Cancer Res 2019;8:255-61.
DOI: https://doi.org/10.21037/tcr.2019.01.26
Sahoo R, Vidya Harini V, Chitti Babu V, et al. Screening for EGFR mutations in lung cancer, a report from India. Lung Cancer 2011;73:316-9.
DOI: https://doi.org/10.1016/j.lungcan.2011.01.004
Noronha V, Prabhash K, Thavamani A, et al. EGFR mutations in Indian lung cancer patients: Clinical correlation and outcome to EGFR targeted therapy. PLoS One 2013;8:e61561.
DOI: https://doi.org/10.1371/journal.pone.0061561
Venkataram R, Arjuna S, Hosmane GB, Chakraborty A. Quantitative analysis of cell-free DNA by droplet digital PCR reveals the presence of EGFR mutations in non-malignant lung pathologies. Monaldi Arch Chest Dis 2021;91:1748.
DOI: https://doi.org/10.4081/monaldi.2021.1748
Siegele BJ, Shilo K, Chao BH, et al. Epidermal growth factor receptor (EGFR) mutations in small cell lung cancers: two cases and a review of the literature. Lung Cancer 2016;95:65–72.
DOI: https://doi.org/10.1016/j.lungcan.2016.02.012
Petricevic B, Tay RY, Califano R. Treatment resistant de novo epidermal growth factor receptor (EGFR)-mutated small cell lung cancer. Eur Oncol Hematol Rev 2018;14:84–6.
DOI: https://doi.org/10.17925/EOH.2018.14.2.84
Okamoto I, Araki J, Suto R, et al. EGFR mutation in gefitinib responsive small-cell lung cancer. Ann Oncol 2006;17:1028–9.
DOI: https://doi.org/10.1093/annonc/mdj114
Zakowski MF, Ladanyi M, Kris MG. Memorial sloan-kettering cancer center lung cancer oncogenome group. EGFR mutations in small-cell lung cancers in patients who have never smoked. N Engl J Med 2006;355:213–5.
DOI: https://doi.org/10.1056/NEJMc053610
Araki J, Okamoto I, Suto R, et al. Efficacy of the tyrosine kinase inhibitor gefitinib in a patient with metastatic small cell lung cancer. Lung Cancer 2005;48:141–4.
DOI: https://doi.org/10.1016/j.lungcan.2004.10.012
Le X, Desai NV, Majid A, et al. De novo pulmonary small cell carcinomas and large cell neuroendocrine carcinomas harbouring EGFR mutations: lack of response to EGFR inhibitors. Lung Cancer 2015;88:70–3.
DOI: https://doi.org/10.1016/j.lungcan.2015.02.003
Zhong J, Li L, Wang Z, et al. Potential resistance mechanisms revealed by targeted sequencing from lung adenocarcinoma patients with primary resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). J Thorac Oncol 2017;12:1766–78.
DOI: https://doi.org/10.1016/j.jtho.2017.07.032
How to Cite
Venkataram, Rajesh, Vijith Shetty, Kishan Prasad, Sonam Kille, Teerthanath Srinivas, and Anirban Chakraborty. 2022. “Detection of Clinically-Relevant <em>EGFR< em> Variations in <em>de novo< em> Small Cell Lung Carcinoma by Droplet Digital PCR”. Monaldi Archives for Chest Disease 93 (2). https://doi.org/10.4081/monaldi.2022.2280.
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