用于非小细胞肺癌早期检测和疾病监测的ctDNA多基因面板的可行性

IF 4.5 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology
Giovanna Maria Stanfoca Casagrande, Marcela de Oliveira Silva, Mariana Bisarro Dos Reis, Rodrigo de Oliveira Cavagna, Luciane Sussuchi, Icaro Alves Pinto, Natalia Zampieri Pontes, Rodrigo Sampaio Chiarantano, Flavio Augusto Ferreira da Silva, Pedro de Marchi, Letícia Ferro Leal, Rui M Reis
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引用次数: 0

摘要

液体活检中可操作突变的检测是非小细胞肺癌(NSCLC)患者精确肿瘤学的重要工具。我们使用巴西NSCLC患者循环肿瘤DNA (ctDNA)的多基因面板评估了可操作的改变。我们分析了来自30例非小细胞肺癌患者的32个样本,包括来自肺癌筛查项目的4个样本。使用Oncomine Lung cfDNA Assay进行ctDNA分离和文库制备,其中包含11个可操作基因,并在Ion S5测序仪上测序。使用IonReporter 5.20软件进行变体调用。中位读覆盖率为80967,检出限为0.1%。TP53(40.6%)、KRAS(28.1%)和EGFR(12.5%)是最常见的突变基因,特别是在先前接受过治疗的患者中。BRAF、MAP2K1、PIK3CA和ALK突变的频率较低(分别为6.2%、3.1%、3.1%和3.1%)。在先前接受过治疗的患者中发现了与耐药相关的EGFR p.T790M突变,在诊断前在无症状患者中发现了TP53 p.R248Q突变。NRAS、ROS1和MET基因未见变异。我们的数据显示,这种商业化的NGS面板可以检测出可操作的突变,从而实现早期检测、治疗监测和疾病监测。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Feasibility of a ctDNA multigenic panel for non-small-cell lung cancer early detection and disease surveillance.

The detection of actionable mutations in liquid biopsies is a crucial tool for precision oncology in patients with non-small-cell lung cancer (NSCLC). We evaluated actionable alterations using a multigene panel in circulating tumor DNA (ctDNA) from Brazilian NSCLC patients. We analyzed 32 samples from 30 patients with NSCLC, including four samples from a lung cancer screening program. ctDNA isolation and library preparation were performed using the Oncomine Lung cfDNA Assay, which covers 11 actionable genes, and sequenced on an Ion S5 Sequencer. The IonReporter 5.20 software was used for variant calling. Median read coverage reached 80 967, with a detection limit of 0.1%. TP53 (40.6%), KRAS (28.1%), and EGFR (12.5%) were the most frequently mutated genes, particularly in patients who had previously received treatment. BRAF, MAP2K1, PIK3CA, and ALK mutations were observed at lower frequencies (6.2%, 3.1%, 3.1%, and 3.1%, respectively). The EGFR p.T790M mutations related to resistance were identified in a patient who had been previously treated, and the TP53 p.R248Q mutation was discovered in an asymptomatic patient before diagnosis. No variants were observed in NRAS, ROS1, and MET genes. Our data showed that this commercial NGS panel could detect actionable mutations, enabling early detection, treatment monitoring, and disease surveillance.

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来源期刊
Molecular Oncology
Molecular Oncology Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
11.80
自引率
1.50%
发文量
203
审稿时长
10 weeks
期刊介绍: Molecular Oncology highlights new discoveries, approaches, and technical developments, in basic, clinical and discovery-driven translational cancer research. It publishes research articles, reviews (by invitation only), and timely science policy articles. The journal is now fully Open Access with all articles published over the past 10 years freely available.
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