NUP214 fusion genes in acute leukemias: genetic characterization of rare cases

Marta Brunetti; Kristin Andersen; Signe Spetalen; Andrea Lenartova; Liv Toril Nygård Osnes; Helen Vålerhaugen; Sverre Heim; Francesca Micci

doi:10.3389/fonc.2024.1371980

NUP214 fusion genes in acute leukemias: genetic characterization of rare cases

Front Oncol. 2024 Mar 20:14:1371980. doi: 10.3389/fonc.2024.1371980. eCollection 2024.

Authors

Marta Brunetti¹, Kristin Andersen¹, Signe Spetalen^{2

3}, Andrea Lenartova⁴, Liv Toril Nygård Osnes⁵, Helen Vålerhaugen², Sverre Heim¹, Francesca Micci¹

Affiliations

¹ Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
² Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
³ Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
⁴ Department of Haematology, Oslo University Hospital, Oslo, Norway.
⁵ Department of Immunology, Oslo University Hospital, Oslo, Norway.

Abstract

Introduction: Alterations of the NUP214 gene (9q34) are recurrent in acute leukemias. Rearrangements of chromosomal band 9q34 targeting this locus can be karyotypically distinct, for example t(6;9)(p22;q34)/DEK::NUP214, or cryptic, in which case no visible change of 9q34 is seen by chromosome banding.

Methods: We examined 9 cases of acute leukemia with NUP214 rearrangement by array Comparative Genomic Hybridization (aCGH), reverse-transcription polymerase chain reaction (RT-PCR), and cycle sequencing/Sanger sequencing to detect which fusion genes had been generated.

Results: The chimeras DEK::NUP214, SET::NUP214, and NUP214::ABL1 were found, only the first of which can be readily detected by karyotyping.

Discussion: The identification of a specific NUP214 rearrangement is fundamental in the management of these patients, i.e., AMLs with DEK::NUP214 are classified as an adverse risk group and might be considered for allogenic transplant. Genome- and/or transcriptome-based next generation sequencing (NGS) techniques can be used to screen for these fusions, but we hereby present an alternative, step-wise procedure to detect these rearrangements.

Keywords: 9q34-NUP214; acute leukemias; array comparative genomic hybridization; cytogenetics; fluorescence in situ hybridization; fusion gene; rare leukemias.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was funded by The Norwegian Radium Hospital Foundation (Radiumhospitalets legater).