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Lymphoma

Insights into the multistep transformation process of lymphomas: IgH-associated translocations and tumor suppressor gene mutations in clonally related composite Hodgkin's and non-Hodgkin's lymphomas

Leukemia volume 19, pages 1452–1458 (2005)Cite this article

Abstract

Clonally related composite lymphomas of Hodgkin's lymphoma (HL) and Non-Hodgkin's lymphoma (NHL) represent models to study the multistep transformation process in tumorigenesis and the development of two distinct tumors from a shared precursor. We analyzed six such lymphomas for transforming events. The HLs were combined in two cases with follicular lymphoma (FL), and in one case each with B-cell chronic lymphocytic leukemia, splenic marginal zone lymphoma, mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL). In the HL/FL and HL/MCL combinations, BCL2/IGH and CCND1/IGH translocations, respectively, were detected in both the HL and NHL. No mutations were found in the tumor suppressor genes FAS, NFKBIA and ATM. The HL/DLBCL case harbored clonal replacement mutations of the TP53 gene on both alleles exclusively in the DLBCL. In conclusion, we present the first examples of molecularly verified IgH-associated translocations in HL, which also show that BCL2/IGH or CCND1/IGH translocations can represent early steps in the pathogenesis of composite HL/FL or HL/MCL. The restriction of the TP53 mutations to the DLBCL in the HL/DLBCL case exemplifies a late transforming event that presumably happened in the germinal center and affected the fate of a common lymphoma precursor cell towards development of a DLBCL.

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Acknowledgements

We are grateful to Julia Jesdinsky, Michaela Fahrig, Yvonne Blum and Kerstin Heise for excellent technical assistance. We thank Malcolm Taylor for helpful discussions. This work was supported by the Deutsche Krebshilfe, Mildred Scheel-Stiftung (70-3173-Tr3), the IFORES program of the University of Essen, Medical School, the Swiss National Science Foundation and stipends from the Swedish Society for Medical Research and the Werner-Gren Foundations to RR.

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  1. R Schmitz, C Renné and R Rosenquist: These authors contributed equally to this work

Authors and Affiliations

  1. Institute for Cell Biology (Tumor Research), University of Duisburg-Essen Medical School, Essen, Germany

    R Schmitz, V Distler & R Küppers

  2. Department of Pathology, University of Frankfurt, Frankfurt, Germany

    C Renné, V Distler, A Bräuninger & M-L Hansmann

  3. Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden

    R Rosenquist

  4. Institute of Clinical Pathology, University Hospital, Zürich, Switzerland

    M Tinguely

  5. Department of Pathology, University of Verona, Verona, Italy

    F Menestrina & M Lestani

  6. Cancer Research, UK Institute for Cancer Studies, University of Birmingham, Edgbaston, UK

    T Stankovic & B Austen

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Schmitz, R., Renné, C., Rosenquist, R. et al. Insights into the multistep transformation process of lymphomas: IgH-associated translocations and tumor suppressor gene mutations in clonally related composite Hodgkin's and non-Hodgkin's lymphomas. Leukemia 19, 1452–1458 (2005). https://doi.org/10.1038/sj.leu.2403841

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