Diagnosis of fusion genes using targeted RNA sequencing
Diagnosis of fusion genes using targeted RNA sequencing
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DOI：
10.1038/s41467-019-09374-9
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发表时间：
2019-03-27
影响因子：
16.6
通讯作者：
Blackburn, James
中科院分区：
文献类型：
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作者：
Heyer, Erin E.;Deveson, Ira W.;Blackburn, James
融合基因是癌症的主要原因。它们的快速和准确的诊断可以为临床行动提供信息，但目前的分子诊断分析在分辨率和吞吐量方面受到限制。在这里，我们证明了靶向RNA测序(RNAseq)可以克服这些限制。首先，我们通过使用尖峰标准和细胞系来优化实验室和生物信息学变量，从而确定与靶向RNAseq的融合基因检测既敏感又定量。接下来，我们分析了一个临床患者队列，并将总体融合基因诊断率从传统方法的63%提高到靶向RNAseq的76%，同时显示出患者样本与先前诊断的高度一致性。最后，我们证明了靶向RNAseq通过同时测量基因表达水平和分析免疫受体谱系提供了额外的优势。我们预计靶向RNAseq将改善临床融合基因的检测，它的日益使用将提供对融合基因生物学的更深层次的理解。
Fusion genes are a major cause of cancer. Their rapid and accurate diagnosis can inform clinical action, but current molecular diagnostic assays are restricted in resolution and throughput. Here, we show that targeted RNA sequencing (RNAseq) can overcome these limitations. First, we establish that fusion gene detection with targeted RNAseq is both sensitive and quantitative by optimising laboratory and bioinformatic variables using spike-in standards and cell lines. Next, we analyse a clinical patient cohort and improve the overall fusion gene diagnostic rate from 63% with conventional approaches to 76% with targeted RNAseq while demonstrating high concordance for patient samples with previous diagnoses. Finally, we show that targeted RNAseq offers additional advantages by simultaneously measuring gene expression levels and profiling the immune-receptor repertoire. We anticipate that targeted RNAseq will improve clinical fusion gene detection, and its increasing use will provide a deeper understanding of fusion gene biology.