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. 2005 Aug;19(8):1452-8. doi: 10.1038/sj.leu.2403841.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / pathology
  • Clone Cells
  • Cyclin D1 / genetics
  • Genes, Tumor Suppressor*
  • Genes, bcl-2
  • Hodgkin Disease / pathology
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Lymphoma / etiology
  • Lymphoma / genetics
  • Lymphoma / pathology*
  • Lymphoma, Non-Hodgkin / pathology
  • Mutation*
  • Translocation, Genetic*
  • Tumor Suppressor Protein p53 / genetics


  • Immunoglobulin Heavy Chains
  • Tumor Suppressor Protein p53
  • Cyclin D1