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BioMed Research International
Volume 2018, Article ID 9010353, 6 pages
https://doi.org/10.1155/2018/9010353
Research Article

Mutational Profiling of Non-Small-Cell Lung Cancer Resistant to Osimertinib Using Next-Generation Sequencing in Chinese Patients

1Department of Radiotherapy, Qingdao Cancer Hospital, Qingdao 266042, China
2Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266002, China
3Department of Oncology, The Affiliated Qingdao Central Hospital of Qingdao University, Qingdao 266042, China
4Oncology Genemic, Geneplus Beijing, Beijing 100010, China

Correspondence should be addressed to Youxin Ji; moc.liamg@ij987654321

Received 19 December 2017; Revised 23 January 2018; Accepted 6 February 2018; Published 11 March 2018

Academic Editor: Valli De Re

Copyright © 2018 Keke Nie et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose. To identify the somatic mutated genes for optimal targets of non-small-cell lung cancer after resistance to osimertinib treatment. Patients and Methods. Study patients all had advanced lung adenocarcinoma and acquired resistance to osimertinib as a second- or third-line treatment. These patients had harboring EGFR T790M mutation before osimertinib treatment, which was confirmed by Amplification Refractory Mutation System (ARMS) PCR or Next-Generation Sequencing (NGS). After resistance to osimertinib treatment, tumor tissue was collected by core needle biopsy. DNA was extracted from 15 × 5 um sliced section of formalin-fixed paraffin-embedded (FFPE) material and NGS was done. The genetic changes were analyzed. Results. A total of 9 Chinese patients were studied, 5 females and 4 males, age 51–89 years. After progression with osimertinib treatment, core needle biopsy was performed and next-generation sequencing was performed. Nine patients had harboring 62 point mutations, 2 altered gene copies, 2 amplifications, and 1 EML4-ALK gene fusion. No MET or HER2 amplification was found in this cohort study. Nine patients still maintained initial EGFR 19 del or L858R activating mutations, while 7 of them kept EGFR T790M mutations. Among the 7 patients, 5 had secondary EGFR C797S and/or C797G mutations, which all happened in the same allele with T790M mutation. All patients were treated with targets therapies, chemotherapy, or best supportive care (BSC) in accordance with NGS genetic results and patients’ performance status; 7 of them are still alive and 2 of them died of disease progression at last follow-up. Conclusions. EGFR C797S/G mutation and the same one presented on the same allele with EGFR T790M mutation were the most common mutation feature and played a key role in resistance to osimertinib in Chinese patients with NSCLC. Tumor cells losing T790M mutation and maintaining EGFR activating mutation might benefit from first-generation EGFR-TKI treatment.