Highly sensitive fusion detection using plasma cell-free RNA in non-small-cell lung cancers.

Highly sensitive fusion detection using plasma cell-free RNA in non-small-cell lung cancers.
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DOI:
10.1111/cas.15084
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发表时间:
2021-10
期刊:
影响因子:
5.7
通讯作者:
Mano H
Mano H
中科院分区:
医学2区
文献类型:
--
作者:
Hasegawa N;Kohsaka S;Kurokawa K;Shinno Y;Takeda Nakamura I;Ueno T;Kojima S;Kawazu M;Suehara Y;Ishijima M;Goto Y;Kojima Y;Yonemori K;Hayashi T;Saito T;Shukuya T;Takahashi F;Takahashi K;Mano H

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ALK、ROS 1和RET激酶融合是非小细胞肺癌(NSCLC)中酪氨酸激酶抑制剂(TKI)的重要预测生物标志物。无细胞DNA(cfDNA)分析提供了一种非侵入性方法来识别肿瘤细胞中的基因变化。本研究试图使用cfRNA和cfDNA来鉴定融合基因。建立了使用cfRNA检测融合基因的可靠方案,并在来自20例融合阳性NSCLC病例的30份样本中评估了分析有效性和临床有用性。将基于cfRNA的测定结果与组织活检和基于cfDNA的液体活检(Guardant 360血浆下一代测序[NGS]测定)进行比较。基于cfRNA的检测的总体灵敏度为26.7%(8/30),基于cfDNA的检测的总体灵敏度为16.7%(3/18)。当分析仅限于在化疗初治或疾病进展状态下采集的样本,并且两种检测方法均可用时,基于cfRNA的检测方法的灵敏度为77.8%(7/9),基于cfDNA的检测方法的灵敏度为33.3%(3/9)。cfRNA中的融合基因鉴定与治疗反应相关。这些结果表明,拟定的cfRNA检测试剂盒是一种有用的诊断检测,可用于组织不足的患者,以促进一线治疗的有效给药,并且是监测NSCLC进展的有用工具,可考虑进行二线治疗。在20例融合阳性NSCLC病例中评价了基于cfRNA和cfDNA的检测。cfRNA法检测基因融合的能力上级优于cfDNA法。cfRNA测定的结果与治疗效果一致。
ALK, ROS1, and RET kinase fusions are important predictive biomarkers of tyrosine kinase inhibitors (TKIs) in non‐small‐cell lung cancer (NSCLC). Analysis of cell‐free DNA (cfDNA) provides a noninvasive method to identify gene changes in tumor cells. The present study sought to use cfRNA and cfDNA for identifying fusion genes. A reliable protocol was established to detect fusion genes using cfRNA and assessed the analytical validity and clinical usefulness in 30 samples from 20 cases of fusion‐positive NSCLC. The results of cfRNA‐based assays were compared with tissue biopsy and cfDNA‐based liquid biopsy (Guardant360 plasma next‐generation sequencing [NGS] assay). The overall sensitivity of the cfRNA‐based assay was 26.7% (8/30) and that of cfDNA‐based assay was 16.7% (3/18). When analysis was limited to the samples collected at chemo‐naïve or progressive disease status and available for both assays, the sensitivity of the cfRNA‐based assay was 77.8% (7/9) and that of cfDNA‐based assay was 33.3% (3/9). Fusion gene identification in cfRNA was correlated with treatment response. These results suggest that the proposed cfRNA assay is a useful diagnostic test for patients with insufficient tissues to facilitate effective administration of first‐line treatment and is a useful tool to monitor the progression of NSCLC for consideration of second‐line treatments. cfRNA‐ and cfDNA‐based assays are evaluated in 20 cases of fusion‐positive NSCLC. cfRNA assay was superior to cfDNA assay for the detection of gene fusions. The results of the cfRNA assay were consistent with the therapeutic effect.
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发表时间: 2016-12
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影响因子: 51.1
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