Characterizing false-positive fluorescence in situ hybridization results by mate-pair sequencing in a patient with chronic myeloid leukemia and progression to myeloid blast crisis Article

Full Text via DOI: 10.1016/j.cancergen.2020.02.008 PMID: 32272434 Web of Science: 000534631300005

Cited authors

  • Lopes, Jaime L.; Webley, Matthew; Pitel, Beth A.; Pearce, Kathryn E.; Smadbeck, James B.; Johnson, Sarah H.; Vasmatzis, George; Sukov, William R.; Greipp, Patricia; Hoppman, Nicole L.; Ketterling, Rhett P.; Baughn, Linda B.; Finn, Laura; Peterson, Jess F.


  • Traditional cytogenetic testing methodologies, including conventional chromosome analysis and fluorescence in situ hybridization (FISH), are invaluable for the detection or recurrent genetic abnormalities in various hematologic malignancies. However, technological advances, including a novel next-generation sequencing technique termed mate-pair sequencing (MPseq), continue to revolutionize the field of cytogenetics by enabling the characterization of structural variants at a significantly higher resolution compared to traditional methodologies. To illustrate the power of MPseq, we present a 27-year-old male diagnosed with chronic myeloid leukemia in myeloid blast crisis with multiple chromosomal abnormalities observed in all 20 metaphases from a peripheral blood specimen, including t(9;22)(q34;q11.2) and t(4;11)(q12;p15). Suspicious of a novel NUP98/PDGFRA fusion [t(4;11)(q12;p15)], break-apart FISH probe sets for the PDGFRA (4q12) and NUP98 (11p15.4) gene regions were performed and were both positive in approximately 86% of 200 interphase nuclei. However, subsequent MPseq testing revealed breakpoints located within the NUP98 gene and within an intergenic region (4q12) located between the CHIC2 and PDGFRA genes, indicating this 4;11 translocation does not result in the predicted NUP98/PDGFRA gene fusion as inferred from FISH and conventional chromosome results. This case demonstrates the clinical utility of MPseq, particularly for characterizing novel gene fusion events which may ultimately identify a false-positive FISH result. (C) 2020 Elsevier Inc. All rights reserved.


Publication date

  • 2020

Published in


International Standard Serial Number (ISSN)

  • 2210-7762

Start page

  • 48

End page

  • 51


  • 243