A Comprehensive Circulating Tumor DNA Assay for Detection of Translocation and Copy-Number Changes in Pediatric Sarcomas.
A Comprehensive Circulating Tumor DNA Assay for Detection of Translocation and Copy-Number Changes in Pediatric Sarcomas.
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DOI：
10.1158/1535-7163.mct-20-0987
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发表时间：
2021-10
影响因子：
5.7
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中科院分区：
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大多数循环肿瘤DNA（ctDNA）测定旨在检测复发性突变。儿童肉瘤很少有复发性突变，而是以易位和拷贝数变化为特征。我们应用深度测序癌症个性化分析（CAPP-Seq）检测最常见的儿科肉瘤中发现的易位。我们还将ichorCNA应用于来自我们的杂交捕获的组合脱靶读段，以同时检测拷贝数改变（CNA）。我们分析了17例儿童肉瘤患者的64份前瞻性血浆样本。在13名患者的治疗前血浆中检测到易位，并在12名患者中通过肿瘤测序证实。其中两名患者的ctDNA中有复杂的染色体重排的证据。我们还检测了7例患者治疗前血浆中的拷贝数变化。我们发现ctDNA水平与转移状态和临床反应相关。此外，我们在复发前检测到ctDNA水平升高是临床上明显的，证明了我们的测定的高灵敏度。该测定可用于同时检测儿童肉瘤患者血浆中的易位和CNA。虽然我们描述了我们在儿科肉瘤中的经验，但这种方法可以应用于由结构变异驱动的其他肿瘤。
Most circulating tumor DNA (ctDNA) assays are designed to detect recurrent mutations. Pediatric sarcomas share few recurrent mutations but rather are characterized by translocations and copy-number changes. We applied Cancer Personalized Profiling by deep Sequencing (CAPP-Seq) for detection of translocations found in the most common pediatric sarcomas. We also applied ichorCNA to the combined off-target reads from our hybrid capture to simultaneously detect copy-number alterations (CNA). We analyzed 64 prospectively collected plasma samples from 17 patients with pediatric sarcoma. Translocations were detected in the pretreatment plasma of 13 patients and were confirmed by tumor sequencing in 12 patients. Two of these patients had evidence of complex chromosomal rearrangements in their ctDNA. We also detected copy-number changes in the pretreatment plasma of 7 patients. We found that ctDNA levels correlated with metastatic status and clinical response. Furthermore, we detected rising ctDNA levels before relapse was clinically apparent, demonstrating the high sensitivity of our assay. This assay can be utilized for simultaneous detection of translocations and CNAs in the plasma of patients with pediatric sarcoma. While we describe our experience in pediatric sarcomas, this approach can be applied to other tumors that are driven by structural variants.