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Molecular cytogenetic characterization of t(14;19)(q32;p13), a new recurrent translocation in B cell malignancies

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Abstract

Translocations involving an immunoglobulin (IG) locus are a recurring theme in B cell neoplasia. The rearrangements lead to the joining of an IG gene with a (proto)oncogene, whereby the latter comes under the influence of transcription-stimulating sequences in the constitutively active IG locus resulting in deregulation of the oncogene and neoplastic growth. We present here three cases of B cell neoplasia that showed a t(14;19)(q32;p13) by karyotypic analysis. Detailed molecular cytogenetic characterization of the breakpoints on chromosomes 14 and 19 in the two cases from which extra material was available, demonstrated the involvement of the immunoglobulin heavy-chain (IGH@)-variable region on chromosome 14 in both and, in one case, that the breakpoint was within the BRD4 gene on chromosome 19. Against the background of what one knows about IGH@ involvement in lymphatic malignancies, it is difficult to envisage a fusion gene with qualitatively altered protein product as the crucial pathogenetic outcome of the translocation. In spite of the fact that we found BRD4 split by the t(14;19)(q32;p13) in one of the two informative cases, we cannot be sure that this was the pathogenetically relevant target gene. Other pathogenetic possibilities could be deregulation of the neighboring NOTCH3 and/or ABHD9 genes, located distal to BRD4 in 19p13.

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Acknowledgments

This work was supported by grants from the Norwegian Cancer Society, COST Action B-19—Molecular cytogenetics of solid tumors—Short-term Scientific Mission programme, the Gunnar Nilsson’s Cancer Foundation, and The Swedish Children’s Cancer Foundation.

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Authors and Affiliations

  1. Department of Medical Genetics, Rikshospitalet-Radiumhospitalet Medical Centre (Montebello), 0310, Oslo, Norway

    Francesca Micci & Sverre Heim

  2. Department of Clinical Genetics, University Hospital, Lund, Sweden

    Ioannis Panagopoulos

  3. Medical Department, Division of Hematology, Rikshospitalet-Radiumhospitalet Medical Centre (Gaustad), Oslo, Norway

    Geir E. Tjønnfjord

  4. Department of Oncology, Rikshospitalet-Radiumhospitalet Medical Centre (Montebello), Oslo, Norway

    Arne Kolstad

  5. Department of Pathology, Rikshospitalet-Radiumhospitalet Medical Centre (Montebello), Oslo, Norway

    Jan Delabie & Klaus Beiske

  6. Faculty of Medicine, University of Oslo, Oslo, Norway

    Geir E. Tjønnfjord & Sverre Heim

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  1. Francesca Micci
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  2. Ioannis Panagopoulos
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Correspondence to Francesca Micci.

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Micci, F., Panagopoulos, I., Tjønnfjord, G.E. et al. Molecular cytogenetic characterization of t(14;19)(q32;p13), a new recurrent translocation in B cell malignancies. Virchows Arch 450, 559–565 (2007). https://doi.org/10.1007/s00428-007-0407-6

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  • DOI: https://doi.org/10.1007/s00428-007-0407-6

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