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基于液体活检分析的黎巴嫩 TKI 治疗耐药性肺癌患者 T790M 突变的流行率:来自主要三级护理中心的首次报告。

Prevalence of T790M mutation among TKI-therapy resistant Lebanese lung cancer patients based on liquid biopsy analysis: a first report from a major tertiary care center.

机构信息

Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.

Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, PO BOX 11-0236, Beirut, Lebanon.

出版信息

Mol Biol Rep. 2019 Aug;46(4):3671-3676. doi: 10.1007/s11033-019-04797-5. Epub 2019 May 30.

Abstract

Lung adenocarcinoma patients have variable prognosis due to many factors. Detection of epidermal growth factor receptor (EGFR) activating mutations is one of the factors that implies the need for initiating a first-line EGFR tyrosine kinase inhibitor (TKI) treatment. However, T790M resistance mutation emergence during treatment accounts for most EGFR-TKI drug resistance. The traditional sample taken for T790M mutation analysis is tissue biopsy, but its numerous disadvantages have introduced liquid biopsy as a preferred method for testing. We studied the prevalence of T790M mutation among pulmonary adenocarcinoma patients in Lebanese patients based on liquid biopsy testing the circulating tumor DNA (ctDNA). We have reviewed the laboratory charts of 52 patients who developed resistance on treatment and referred to AUBMC for EGFR T790M Liquid Biopsy to analyze the mutational analysis results for EGFR T790M. In total, 82.6% of the tested lung cancer patients were positive for a specific EGFR mutation. Among these patients, a total 26.9% were positive for T790M, which is comparable to the international prevalence of this mutation. However, for those cases who developed resistance with circulating DNA showing an EGFR mutation, 50% were positive for T790M that is also comparable to the international literature. This is the first report from Lebanon to discuss the prevalence of T790M mutation using liquid biopsy among Lebanese population. An important landmark molecular epidemiology study that will be a reference to all oncologists in Lebanon and the region in assessing the potential for targeted therapy options in the country. In addition, the data will be of an asset to the building international literature related to this disease.

摘要

肺腺癌患者由于多种因素预后不同。表皮生长因子受体(EGFR)激活突变的检测是需要启动一线 EGFR 酪氨酸激酶抑制剂(TKI)治疗的因素之一。然而,治疗过程中 T790M 耐药突变的出现是 EGFR-TKI 药物耐药的主要原因。传统的 T790M 突变分析样本是组织活检,但它存在许多缺点,这促使液体活检成为首选的检测方法。我们基于循环肿瘤 DNA(ctDNA)的液体活检检测,研究了黎巴嫩肺腺癌患者中 T790M 突变的流行情况。我们回顾了在治疗中发生耐药并转至 AUBMC 进行 EGFR T790M 液体活检的 52 名患者的实验室图表,以分析 EGFR T790M 的突变分析结果。总共,82.6%的肺癌患者的特定 EGFR 突变呈阳性。在这些患者中,共有 26.9%的患者 T790M 呈阳性,这与该突变的国际流行率相当。然而,对于那些具有循环 DNA 显示 EGFR 突变的耐药病例,50%的患者 T790M 呈阳性,这与国际文献也相当。这是黎巴嫩首次使用液体活检报告黎巴嫩人群中 T790M 突变的流行率。这是一项重要的分子流行病学研究,将为黎巴嫩和该地区的所有肿瘤学家提供参考,以评估该国靶向治疗选择的潜力。此外,这些数据将为建立与该疾病相关的国际文献提供支持。

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