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

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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.

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Acknowledgements

The authors would like to thank all the laboratory staff at the Pathology and Laboratory Medicine (PALM), London Health Science Center for their significant contributions towards this study.

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Author notes

  1. Pratibha Bhai, Cyrus C. Hsia and Laila C. Schenkel contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada

    Pratibha Bhai, Laila C. Schenkel, Benjamin D. Hedley, Michael A. Levy, Jennifer Kerkhof, Alan Stuart, Hanxin Lin, Robert Broadbent, Shirley Nan, Ping Yang & Bekim Sadikovic

  2. Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada

    Pratibha Bhai, Laila C. Schenkel, Michael A. Levy, Jennifer Kerkhof, Stephanie Santos, Alan Stuart, Hanxin Lin & Bekim Sadikovic

  3. Division of Hematology, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada

    Cyrus C. Hsia, Anargyros Xenocostas & Ian Chin-Yee

  4. Victoria Hospital, London Health Sciences Centre, 800 Commissioners Road East, Room E6‐211, London, ON, N6A 5W9, Canada

    Ian Chin-Yee

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  1. Pratibha Bhai
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Corresponding authors

Correspondence to Ian Chin-Yee or Bekim Sadikovic.

Ethics declarations

Ethics Approval and Consent to Participate

Not applicable.

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Not applicable.

Availability of Data and Material

All data generated or analyzed during this study are included in this published article (and its Online Supplementary Material).

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Competing Interests

The authors declare that they have no competing interests.

Funding

The London Health Sciences Centre Molecular Diagnostics Innovation and Development Fund.

Authors' Contributions

PB, LS, and CH analyzed and interpreted the data, wrote the manuscript, and contributed equally towards this study. CH, IC, BH, and AX contributed in providing patients’ clinical information. MAL, AS, RB, BH, SN, and PB compiled the laboratory data. BS, MAL, HL, PY, JK, and SS contributed towards validation and implementation of the NGS-based assay and manuscript editing. BS and IC planned and executed the study and contributed significantly to writing the manuscript.

Supplementary Information

Below is the link to the electronic supplementary material.

40291_2022_581_MOESM1_ESM.xlsx

Supplementary Table 1: Tier I/II variants identified in all patients tested by NGS and gene coverage by NGS (XLSX 116 KB)

Supplementary Table 2: NGS findings in patients with CCUS and CHIP (XLSX 11 KB)

40291_2022_581_MOESM3_ESM.xlsx

Supplementary Table 3: Frequency of Tier I/II variants n each clinical group in genes grouped based on cellular processes depicted in Figure 1 (XLSX 13 KB)

Supplementary Table 4: NGS findings in patients with AML (XLSX 28 KB)

Supplementary Table 5: NGS findings in patients with MPN (XLSX 28 KB)

Supplementary Table 6: NGS and cytogenetic findings in patients with MDS (XLSX 24 KB)

Supplementary Table 7: NGS findings and clinical details of patients with MPN/MDS (XLSX 20 KB)

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Bhai, P., Hsia, C.C., Schenkel, L.C. et al. Clinical Utility of Implementing a Frontline NGS-Based DNA and RNA Fusion Panel Test for Patients with Suspected Myeloid Malignancies. Mol Diagn Ther 26, 333–343 (2022). https://doi.org/10.1007/s40291-022-00581-7

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