Pratibha Bhai1,2, Cyrus C Hsia3, Laila C Schenkel1,2, Benjamin D Hedley1, Michael A Levy1,2, Jennifer Kerkhof1,2, Stephanie Santos2, Alan Stuart1,2, Hanxin Lin1,2, Robert Broadbent1, Shirley Nan1, Ping Yang1, Anargyros Xenocostas3, Ian Chin-Yee4,5, Bekim Sadikovic6,7. 1. Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. 2. Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada. 3. Division of Hematology, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. 4. Division of Hematology, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. ian.chinyee@lhsc.on.ca. 5. Victoria Hospital, London Health Sciences Centre, 800 Commissioners Road East, Room E6-211, London, ON, N6A 5W9, Canada. ian.chinyee@lhsc.on.ca. 6. Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. bekim.sadikovic@lhsc.on.ca. 7. Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada. bekim.sadikovic@lhsc.on.ca.
Abstract
BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
Authors: Eri Kawata; Benjamin D Hedley; Benjamin Chin-Yee; Anargyros Xenocostas; Alejandro Lazo-Langner; Cyrus C Hsia; Kang Howson-Jan; Ping Yang; Michael A Levy; Stephanie Santos; Pratibha Bhai; Christopher Howlett; Hanxin Lin; Mike Kadour; Bekim Sadikovic; Ian Chin-Yee Journal: Int J Lab Hematol Date: 2021-10-29 Impact factor: 2.877
Authors: Chris Lauber; Nádia Correia; Andreas Trumpp; Michael A Rieger; Anna Dolnik; Lars Bullinger; Ingo Roeder; Michael Seifert Journal: Sci Rep Date: 2020-07-29 Impact factor: 4.379