Development and Clinical Validation of a Large Fusion Gene Panel for Pediatric Cancers
Development and Clinical Validation of a Large Fusion Gene Panel for Pediatric Cancers
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DOI：
10.1016/j.jmoldx.2019.05.006
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发表时间：
2019-09-01
影响因子：
4.1
通讯作者：
Li, Marilyn M.
中科院分区：
文献类型：
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作者：
Chang, Fengqi;Lin, Fumin;Li, Marilyn M.
基因融合是儿科癌症中最常见的基因组改变之一。许多融合编码致癌驱动因子，并在癌症诊断、风险分层和治疗选择中发挥重要作用。我们报告了一个大型定制设计的RNA测序面板，CHOP融合面板，使用锚定多重PCR技术的开发和临床验证。该小组询问了已知参与血液恶性肿瘤和实体瘤中近600种不同融合的106种癌症基因。该面板适用于不同类型的样品，包括福尔马林固定的石蜡包埋样品。该小组表现出出色的分析准确性，在60个儿科肿瘤验证样本上具有100%的灵敏度和特异性。除了鉴定验证样品中的所有已知融合体外，还检测到三种未识别但具有临床意义的融合体。验证后共分析了276例临床病例，在104例病例中确定了51种不同的融合。在这些融合中，有16个在发现时以前没有报道过。这些融合体提供了对临床管理有用的基因组信息。我们的经验表明，CHOP Fusion panel可以准确、高效、经济地检测儿科癌症中绝大多数已知和某些新的临床相关融合基因;该panel为新融合基因的发现提供了一个很好的工具。
Gene fusions are one of the most common genomic alterations in pediatric cancer. Many fusions encode oncogenic drivers and play important roles in cancer diagnosis, risk stratification, and treatment selection. We report the development and clinical validation of a large custom-designed RNA sequencing panel, CHOP Fusion panel, using anchored multiplex PCR technology. The panel interrogates 106 cancer genes known to be involved in nearly 600 different fusions reported in hematological malignancies and solid tumors. The panel works well with different types of samples, including formalin-fixed, paraffin-embedded samples. The panel demonstrated excellent analytic accuracy, with 100% sensitivity and specificity on 60 pediatric tumor validation samples. In addition to identifying all known fusions in the validation samples, three unrecognized, yet clinically significant, fusions were also detected. A total of 276 clinical cases were analyzed after the validation, and 51 different fusions were identified in 104 cases. Of these fusions, 16 were not previously reported at the time of discovery. These fusions provided genomic information useful for clinical management. Our experience demonstrates that CHOP Fusion panel can detect the vast majority of known and certain novel clinically relevant fusion genes in pediatric cancers accurately, efficiently, and cost-effectively; and the panel provides an excellent tool for new fusion gene discovery.