Clinical Utility of Implementing a Frontline NGS-Based DNA and RNA Fusion Panel Test for Patients with Suspected Myeloid Malignancies

Pratibha Bhai; Cyrus C Hsia; Laila C Schenkel; Benjamin D Hedley; Michael A Levy; Jennifer Kerkhof; Stephanie Santos; Alan Stuart; Hanxin Lin; Robert Broadbent; Shirley Nan; Ping Yang; Anargyros Xenocostas; Ian Chin-Yee; Bekim Sadikovic

doi:10.1007/s40291-022-00581-7

Clinical Utility of Implementing a Frontline NGS-Based DNA and RNA Fusion Panel Test for Patients with Suspected Myeloid Malignancies

Mol Diagn Ther. 2022 May;26(3):333-343. doi: 10.1007/s40291-022-00581-7. Epub 2022 Apr 5.

Authors

Pratibha Bhai^#^{1

2}, Cyrus C Hsia^#³, Laila C Schenkel^#^{1

2}, Benjamin D Hedley¹, Michael A Levy^{1

2}, Jennifer Kerkhof^{1

2}, Stephanie Santos², Alan Stuart^{1

2}, Hanxin Lin^{1

2}, Robert Broadbent¹, Shirley Nan¹, Ping Yang¹, Anargyros Xenocostas³, Ian Chin-Yee^{4

5}, Bekim Sadikovic^{6

7}

Affiliations

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.

^# Contributed equally.

PMID: 35381971
DOI: 10.1007/s40291-022-00581-7

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA
Gene Fusion
High-Throughput Nucleotide Sequencing / methods
Humans
Leukemia, Myeloid, Acute* / diagnosis
Leukemia, Myeloid, Acute* / genetics
Mutation
Myelodysplastic Syndromes* / diagnosis
Myelodysplastic Syndromes* / genetics
Myeloproliferative Disorders* / diagnosis
Myeloproliferative Disorders* / genetics
RNA

Substances

RNA
DNA