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A Novel Non-Immunoglobulin (non-Ig)/BCL6 Translocation in Diffuse Large B-Cell Lymphoma Involving Chromosome 10q11.21 Loci and Review on Clinical Consequences of BCL6 Rearrangements

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Pathology & Oncology Research

Abstract

BCL6 rearrangements (3q27) are the most common chromosomal abnormalities in diffuse large B-cell lymphoma (DLBCL), with numerous immunoglobulin (Ig) and non-Ig genes as partners. In DLBCL, the translocations occur predominantly in the “major breakpoint region” encompassing the first noncoding exon and a part of the first intron of BCL6; few cases with “alternative breakpoint cluster” located 245–285 kb 5′ BCL6 were also described. The regulatory sequences of known Ig and non-Ig partners replace the 5′ untranslated region of the BCL6 in the same transcriptional orientation. Contrary to Ig/BCL6 fusions typical by high BCL6 gene expression, in non-Ig/BCL6 translocations were observed unexpectedly low BCL6 mRNA levels. From the clinical point of view, the survival rate of DLBCL patients with non-Ig partners is inferior to those with Ig/BCL6 translocations, suggesting that non-Ig/BCL6 fusion is a poor prognostic indicator. Hereby we provide comprehensive information about known non-Ig translocation partners and clinical consequences of BCL6 rearrangements in DLBCL. Moreover, we describe a novel reciprocal translocation t(3;10) in refractory patient with DLBCL with the breaking points at 5′ untranslated region of BCL6 and 5′ untranslated region of the RASGEF1A gene on chromosome 10q11.21 loci; this rearrangement was associated with low BCL6 and RASGEF1A gene expressions. Our patient harbouring dual chromosomal rearrangement involving BCL2 and BCL6 genes relapsed three-times and died soon; thus, further supporting the notion that non-Ig/BCL6 fusion is a poor prognostic indicator of DLBCL. There is evidence of prognostic value of BCL6 rearrangements also in rituximab era.

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Acknowledgments

This work was supported by the grant of the Ministry of Health of the Czech Republic IGA MZ CR NT11103.

Compliance with Ethical Standards

The authors declare that they have no conflict of interest. Written informed consent was duly obtained from the patient for the publication of this report and its accompanying images. All examinations were performed in accordance with the current version of the Helsinki Declaration and the study was approved by the Ethics Committee of the University Hospital in Olomouc.

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in the study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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    Authors and Affiliations

    1. Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and the University Hospital Olomouc, Hnevotinska 3, 77900, Olomouc, Czech Republic

      Marie Jarosova, Vit Prochazka, Michaela Mikesova, Karel Indrak & Tomas Papajik

    2. Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hnevotinska 3, 77900, Olomouc, Czech Republic

      Eva Kriegova, Petra Schneiderova & Regina Fillerova

    3. Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc and the University Hospital Olomouc, Hnevotinska 3, 77900, Olomouc, Czech Republic

      Patrik Flodr

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    1. Marie Jarosova
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    Correspondence to Marie Jarosova.

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    Marie Jarosova and Eva Kriegova contributed equally to this work.

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    Jarosova, M., Kriegova, E., Schneiderova, P. et al. A Novel Non-Immunoglobulin (non-Ig)/BCL6 Translocation in Diffuse Large B-Cell Lymphoma Involving Chromosome 10q11.21 Loci and Review on Clinical Consequences of BCL6 Rearrangements. Pathol. Oncol. Res. 22, 233–243 (2016). https://doi.org/10.1007/s12253-015-9972-1

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