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Mate pair sequencing improves detection of genomic abnormalities in acute myeloid leukemia
Author(s) -
Aypar Umut,
Smoley Stephanie A.,
Pitel Beth A.,
Pearce Kathryn E.,
Zenka Roman M.,
Vasmatzis George,
Johnson Sarah H.,
Smadbeck James B.,
Peterson Jess F.,
Geiersbach Katherine B.,
Van Dyke Daniel L.,
Thorland Erik C.,
Jenkins Robert B.,
Ketterling Rhett P.,
Greipp Patricia T.,
Kearney Hutton M.,
Hoppman Nicole L.,
Baughn Linda B.
Publication year - 2019
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.13179
Subject(s) - myeloid leukemia , myeloid , medicine , computational biology , leukemia , genetics , biology , cancer research
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.