Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.
Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, Ontario, Canada.
Eur J Haematol. 2019 Sep;103(3):178-189. doi: 10.1111/ejh.13272. Epub 2019 Jul 30.
The diagnosis of hematologic malignancies integrates multiple diagnostic and clinical disciplines. Historically, targeted (single-analyte) genetic testing has been used as reflex to initial prescreening by other diagnostic modalities including flow cytometry, anatomic pathology, and clinical cytogenetics. Given the wide range of mutations associated with hematologic malignancies a DNA/RNA-based NGS panel can provide a more effective and economical approach to comprehensive testing of patients as an initial, tier-1 screen.
Using a cohort of 380 patients, we performed clinical validation of a gene panel designed to assess 40 genes (DNA), and 29 fusion driver genes with over 600 gene fusion partners (RNA), including sample exchange data across three clinical laboratories, and correlation with cytogenetic testing results.
The clinical validation of this technology demonstrated that its accuracy, sensitivity, and specificity are comparable to the majority of targeted single-gene approaches, while assessment of the initial patient cohort data demonstrated a high diagnostic yield of 50.5%.
Implementation of a tier-1 NGS-based protocol for gene panel screening provides a comprehensive alternative to targeted molecular testing in patients with suspected hematologic malignancies, with increased diagnostic yield, scalability, reproducibility, and cost effectiveness, making it ideally suited for implementation in clinical laboratories.
血液系统恶性肿瘤的诊断涉及多个诊断和临床学科。历史上，靶向（单分析物）基因检测一直被用作其他诊断方式（包括流式细胞术、解剖病理学和临床细胞遗传学）初始预筛查的后续检测。鉴于与血液系统恶性肿瘤相关的突变范围广泛，基于 DNA/RNA 的 NGS 面板可为患者的综合检测提供更有效和经济的方法，作为初始的一级筛查。
我们使用了 380 名患者的队列，对一个旨在评估 40 个基因（DNA）和 29 个融合驱动基因及其 600 多个基因融合伙伴（RNA）的基因面板进行了临床验证，包括三个临床实验室之间的样本交换数据以及与细胞遗传学检测结果的相关性。
该技术的临床验证表明，其准确性、灵敏度和特异性与大多数靶向单基因方法相当，而对初始患者队列数据的评估表明诊断率高达 50.5%。
实施基于 NGS 的一级基因面板筛选方案可为疑似血液系统恶性肿瘤患者提供靶向分子检测的综合替代方案，具有更高的诊断率、可扩展性、可重复性和成本效益，非常适合在临床实验室实施。
