Origin of the T790M mutation and its impact on the clinical outcomes of patients with lung adenocarcinoma receiving EGFR-TKIs |
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Authors: | Yujie Dong Zhen Zhou Jianguo Wang Li Ma Zichen Liu Yuxuan Wang Jing Song Shucai Zhang Nanying Che |
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Affiliation: | 1. Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China;2. Department of Radiology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China;3. School of Biomedical Engineering, Capital Medical University, Beijing, 100069, China;4. Department of Medical Engineering, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China;5. Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China;6. Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, China |
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Abstract: | ObjectiveRecently, a low frequency of de novo T790M mutations existing in tumor tissues before TKIs therapy has been reported. However, the origin of T790M and its impact on clinical outcomes is still being debated. This study aimed to use highly sensitive methods to detect T790M before and after TKIs therapy and investigated the correlation of T790M with clinical prognosis.Patients and methodsMatched tumor samples before and after treatment were collected from 61 lung adenocarcinoma (LAC) patients in Beijing Chest Hospital between June 2014 to October 2017. Presence of the T790M mutation was simultaneously detected using amplification refractory mutation system-PCR (ARMS-PCR) assay and droplet digital PCR (ddPCR) assay.ResultsOf the 61 enrolled patients, 46 were candidates for and received TKIs treatment based on their EGFR mutation status. When these samples were assayed, ddPCR identified significantly more T790M mutations than ARMS-PCR (before TKIs treatment: 19.6% (9/46) vs. 2.2% (1/46), P?=?0.040; after TKIs treatment: 78.3% (36/46) vs. 50% (23/46), P?0.001, respectively). Patients with first-line TKIs treatment harboring de novo T790M mutations showed a shorter PFS compared to those without de novo T790M mutations (median, 7.0 months vs. 11.7 months, p?=?0.013). In multivariate analyses, de novo T790M mutation was an independent predictor of PFS in EGFR-mutant patients who received TKIs treatment (p?=?0.031, HR 0.310, 95% CI: 0.107-0.900).ConclusionThe ddPCR assay is an ultra-sensitive method to detect a minor amount of de novo T790M mutations in tumor samples. The de novo T790M mutation is a relatively unfavorable prognosis factor for patients receiving first-line TKIs treatment. |
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Keywords: | Origin T790M Clinical outcome Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) Lung adenocarcinoma |
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