Mate pair sequencing improves detection of genomic abnormalities in acute myeloid leukemia

Umut Aypar, Stephanie A. Smoley, Beth A. Pitel, Kathryn E. Pearce, Roman M. Zenka, George Vasmatzis, Sarah H. Johnson, James B. Smadbeck, Jess F. Peterson, Katherine B. Geiersbach, Daniel L. Van Dyke, Erik C. Thorland, Robert B. Jenkins, Rhett P. Ketterling, Patricia T. Greipp, Hutton M. Kearney, Nicole L. Hoppman, Linda B. Baughn

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Objective: Acute myeloid leukemia (AML) can be subtyped based on recurrent cytogenetic and molecular genetic abnormalities with diagnostic and prognostic significance. Although cytogenetic characterization classically involves conventional chromosome and/or fluorescence in situ hybridization (FISH) assays, limitations of these techniques include poor resolution and the inability to precisely identify breakpoints. Method: We evaluated whether an NGS-based methodology that detects structural abnormalities and copy number changes using mate pair sequencing (MPseq) can enhance the diagnostic yield for patients with AML. Results: Using 68 known abnormal and 20 karyotypically normal AML samples, each recurrent primary AML-specific abnormality previously identified in the abnormal samples was confirmed using MPseq. Importantly, in eight cases with abnormalities that could not be resolved by conventional cytogenetic studies, MPseq was utilized to molecularly define eight recurrent AML-fusion events. In addition, MPseq uncovered two cryptic abnormalities that were missed by conventional cytogenetic studies. Thus, MPseq improved the diagnostic yield in the detection of AML-specific structural rearrangements in 10/88 (11%) of cases analyzed. Conclusion: Utilization of MPseq represents a precise, molecular-based technique that can be used as an alternative to conventional cytogenetic studies for newly diagnosed AML patients with the potential to revolutionize the diagnosis of hematologic malignancies.

Original languageEnglish (US)
Pages (from-to)87-96
Number of pages10
JournalEuropean Journal of Haematology
Volume102
Issue number1
DOIs
StatePublished - Jan 2019

Keywords

  • MPseq
  • acute myeloid leukemia
  • molecular cytogenetics

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'Mate pair sequencing improves detection of genomic abnormalities in acute myeloid leukemia'. Together they form a unique fingerprint.

  • Cite this

    Aypar, U., Smoley, S. A., Pitel, B. A., Pearce, K. E., Zenka, R. M., Vasmatzis, G., Johnson, S. H., Smadbeck, J. B., Peterson, J. F., Geiersbach, K. B., Van Dyke, D. L., Thorland, E. C., Jenkins, R. B., Ketterling, R. P., Greipp, P. T., Kearney, H. M., Hoppman, N. L., & Baughn, L. B. (2019). Mate pair sequencing improves detection of genomic abnormalities in acute myeloid leukemia. European Journal of Haematology, 102(1), 87-96. https://doi.org/10.1111/ejh.13179