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

Research output: Contribution to journalArticle

Authors

  • R Schmitz
  • C Renne
  • R Rosenquist
  • M Tinguely
  • V Distler
  • F Menestrina
  • M Lestani
  • A Brauninger
  • M-L Hansmann
  • R Kuppers

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)1452-1458
Number of pages7
JournalLeukemia
Volume19
Publication statusPublished - 23 Jun 2005

Keywords

  • CCND1, composite lymphoma, Hodgkin's lymphoma