Bhai Pratibha, Hsia Cyrus C, Schenkel Laila C, Hedley Benjamin D, Levy Michael A, Kerkhof Jennifer, Santos Stephanie, Stuart Alan, Lin Hanxin, Broadbent Robert, Nan Shirley, Yang Ping, Xenocostas Anargyros, Chin-Yee Ian, Sadikovic Bekim
Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada.
Mol Diagn Ther. 2022 May;26(3):333-343. doi: 10.1007/s40291-022-00581-7. Epub 2022 Apr 5.
The use of molecular genetic biomarkers is rapidly advancing to aid diagnosis, prognosis, and clinical management of hematological disorders. We have implemented a next-generation sequencing (NGS) assay for detection of genetic variants and fusions as a frontline test for patients suspected with myeloid malignancy. In this study, we summarize the findings and assess the clinical impact in the first 1613 patients tested.
All patients were assessed using NGS based Oncomine Myeloid Research Assay (ThermoFisher) including 40 genes (17 full genes and 23 genes with clinically relevant "hotspot" regions), along with a panel of 29 fusion driver genes (including over fusion 600 partners).
Among 1613 patients with suspected myeloid malignancy, 43% patients harbored at least one clinically relevant variant: 91% (90/100) in acute myeloid leukemia patients, 71.7% (160/223) in myelodysplastic syndrome (MDS), 77.5% (308/397) in myeloproliferative neoplasm (MPN), 83% (34/41) in MPN/MDS, and 100% (40/40) in chronic myeloid leukemia patients. Comparison of NGS and cytogenetics results revealed a high degree of concordance in gene fusion detection.
Our findings demonstrate clinical utility and feasibility of integrating a NGS-based gene mutation and fusion testing assay as a frontline diagnostic test in a large reported cohort of patients with suspected myeloid malignancy, in a clinical laboratory setting. Overlap with cytogenetic test results provides opportunity for testing reduction and streamlining.
分子遗传生物标志物的应用正在迅速发展，以辅助血液系统疾病的诊断、预后评估及临床管理。我们已实施一项二代测序（NGS）检测，用于检测基因变异和融合，作为疑似髓系恶性肿瘤患者的一线检测方法。在本研究中，我们总结了前1613例接受检测患者的结果并评估了其临床影响。
所有患者均使用基于NGS的Oncomine Myeloid Research Assay（赛默飞世尔）进行评估，该检测包括40个基因（17个完整基因和23个具有临床相关“热点”区域的基因），以及一组29个融合驱动基因（包括超过600个融合伴侣）。
在1613例疑似髓系恶性肿瘤患者中，43%的患者至少携带一种临床相关变异：急性髓系白血病患者中为91%（90/100），骨髓增生异常综合征（MDS）患者中为71.7%（160/223），骨髓增殖性肿瘤（MPN）患者中为77.5%（308/397），MPN/MDS患者中为83%（34/41），慢性髓系白血病患者中为100%（40/40）。NGS结果与细胞遗传学结果的比较显示，在基因融合检测方面具有高度一致性。
我们的研究结果表明，在临床实验室环境中，将基于NGS的基因突变和融合检测方法作为一线诊断检测应用于大量疑似髓系恶性肿瘤患者队列具有临床实用性和可行性。与细胞遗传学检测结果的重叠为减少检测和简化流程提供了机会。
