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.

中文翻译：

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用于检测小儿肉瘤易位和拷贝数变化的综合循环肿瘤 DNA 检测

大多数循环肿瘤 DNA (ctDNA) 检测旨在检测复发性突变。小儿肉瘤几乎没有复发性突变，而是以易位和拷贝数变化为特征。我们通过深度测序 (CAPP-Seq) 应用癌症个性化分析来检测最常见的儿科肉瘤中发现的易位。我们还将 ichorCNA 应用于混合捕获的组合脱靶读取，以同时检测拷贝数改变 (CNA)。我们分析了来自 17 名儿童肉瘤患者的 64 份前瞻性收集的血浆样本。在 13 名患者的治疗前血浆中检测到易位，并通过 12 名患者的肿瘤测序证实了易位。其中两名患者的 ctDNA 中有复杂染色体重排的证据。我们还检测了 7 名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，我们在临床上明显复发之前检测到 ctDNA 水平升高，证明了我们检测的高灵敏度。该测定可用于同时检测小儿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方面的经验，但这种方法可以应用于其他由结构变异驱动的肿瘤。该测定可用于同时检测小儿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方面的经验，但这种方法可以应用于其他由结构变异驱动的肿瘤。该测定可用于同时检测小儿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方面的经验，但这种方法可以应用于其他由结构变异驱动的肿瘤。