Novel ZEB2-BCL11B Fusion Gene Identified by RNA-Sequencing in Acute Myeloid Leukemia with t(2;14)(q22;q32)

Synne Torkildsen; Ludmila Gorunova; Klaus Beiske; Geir E Tjønnfjord; Sverre Heim; Ioannis Panagopoulos

doi:10.1371/journal.pone.0132736

Novel ZEB2-BCL11B Fusion Gene Identified by RNA-Sequencing in Acute Myeloid Leukemia with t(2;14)(q22;q32)

PLoS One. 2015 Jul 17;10(7):e0132736. doi: 10.1371/journal.pone.0132736. eCollection 2015.

Authors

Synne Torkildsen¹, Ludmila Gorunova², Klaus Beiske³, Geir E Tjønnfjord⁴, Sverre Heim⁵, Ioannis Panagopoulos²

Affiliations

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

Abstract

RNA-sequencing of a case of acute myeloid leukemia with the bone marrow karyotype 46,XY,t(2;14)(q22;q32)[5]/47,XY,idem,+?4,del(6)(q13q21)[cp6]/46,XY[4] showed that the t(2;14) generated a ZEB2-BCL11B chimera in which exon 2 of ZEB2 (nucleotide 595 in the sequence with accession number NM_014795.3) was fused to exon 2 of BCL11B (nucleotide 554 in the sequence with accession number NM_022898.2). RT-PCR together with Sanger sequencing verified the presence of the above-mentioned fusion transcript. All functional domains of BCL11B are retained in the chimeric protein. Abnormal expression of BCL11B coding regions subjected to control by the ZEB2 promoter seems to be the leukemogenic mechanism behind the translocation.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Base Sequence
Chromosome Aberrations
Chromosome Banding
Chromosomes, Human, Pair 14 / genetics*
Chromosomes, Human, Pair 2 / genetics*
Fatal Outcome
Humans
Leukemia, Myeloid, Acute / genetics*
Male
Molecular Sequence Data
Mutant Chimeric Proteins / genetics*
Oncogene Proteins, Fusion / genetics*
Real-Time Polymerase Chain Reaction
Reproducibility of Results
Sequence Analysis, RNA*
Translocation, Genetic*

Substances

Mutant Chimeric Proteins
Oncogene Proteins, Fusion
ZEB2-BCL11B fusion protein, human

Grants and funding

This work was supported by grants from the Norwegian Cancer Society and the Norwegian Radium Hospital Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.