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Translocations involving 8q24 in Burkitt lymphoma and other malignant lymphomas: a historical review of cytogenetics in the light of todays knowledge

Leukemia volume 23, pages 225–234 (2009)Cite this article

Abstract

Burkitt lymphoma (BL) has a characteristic clinical presentation, morphology, immunophenotype and primary chromosomal aberration, that is, the translocation t(8;14)(q24;q32) or its variants. However, diagnostic dilemmas may arise in daily practice due to overlap of BL with subsets of other aggressive, mature B-cell lymphomas such as diffuse large B-cell lymphomas (DLBCL). Recently, two gene expression studies have described a distinct molecular profile for BL, but also showed the persistence of some cases intermediate between BL and DLBCL. An alternative approach to define BL is to consider (cyto)genetic data, in particular chromosomal abnormalities other than the t(8;14) or its variants. In this review the ‘Mitelman Database of Chromosome Aberrations in Cancer,’ harboring the majority of all published neoplasia-related karyotypes, was explored to define a cytogenetic profile of ‘true’ BL. This core subset of BL showed a very low complexity of chromosomal abnormalities with 40% of the cases having the IG–MYC fusion as the sole abnormality. In the remaining cases, additional recurrent but partially exclusive abnormalities included gains at chromosomes 1q, 7 and 12, and losses of 6q, 13q32–34 and 17p. Within the core subset, no differences were found between pediatric and adult patients. In addition, the genetic profile of the core subset was significantly different from BL with an 8q24 breakpoint not affecting one of the three immunoglobulin loci, BL with a translocation involving 18q21/BCL2, 3q27/BCL6 or 11q13/BCL1, additionally to a breakpoint at 8q24/MYC, and from other morphological types of lymphomas with an 8q24/MYC breakpoint. These groups showed a higher cytogenetic complexity than the core subset of BL. BL without a detectable 8q24/MYC breakpoint might be heterogeneous and deserves further studies. We suggest that, concordant with the WHO classification to be published in 2008, the diagnosis of BL should be restricted to cases with expression of CD10 and BCL6, absence or very weak expression of BCL2 protein, a homogeneously very high proliferation index and a proven IG-MYC translocation without evidence of a chromosomal translocation typical for other lymphoma entities. In addition, a high number of nonspecific cytogenetic abnormalities should suggest need for a critical review of the diagnosis of BL.

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Acknowledgements

RS' research on BL is supported by the Deutsche Krebshilfe and the Kinder-Krebs-Initiative Buchholz, Holm-Seppensen.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands

    E G Boerma & P M Kluin

  2. Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Christian-Albrechts-University, Kiel, Germany

    R Siebert

  3. Institute of Molecular Biology, University of Zurich, Zurich, Switzerland

    M Baudis

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  1. E G Boerma
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  2. R Siebert
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  4. M Baudis
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Correspondence to R Siebert or P M Kluin.

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Dedication: This review is dedicated to the groundbreaking work of Professor Lore Zech on chromosome banding and t(8;14).

Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Boerma, E., Siebert, R., Kluin, P. et al. Translocations involving 8q24 in Burkitt lymphoma and other malignant lymphomas: a historical review of cytogenetics in the light of todays knowledge. Leukemia 23, 225–234 (2009). https://doi.org/10.1038/leu.2008.281

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