Genetic instability is associated with histological transformation of follicle center lymphoma

M. Nagy, M. Balázs, Z. Ádám, Z. Petkó, B. Tímár, Z. Szereday, T. László, R. A. Warnke, A. Matolcsy

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Abstract

Follicle center lymphoma (FCL) is an indolent B cell non-Hodgkin's lymphoma (NHL) characterized genetically by the t(14;18) translocation. Histological transformation and clinical progression of FCLs are frequently associated with secondary genetic alterations at both nucleic acid and chromosomal levels. To determine the type and pattern of genomic instability occurring in histological transformation of FCLs and the role of DNA mismatch repair defects in this procedure, we have performed microsatellite analysis, comparative genomic hybridization (CGH) and mutational analysis of hMLH1 and hMSH2 genes on serial biopsy specimens from patients with FCL transformed to diffuse large cell lymphoma (DLCL). Paired biopsy samples of eight patients were analyzed for microsatellite instability and structural alterations for hMLH1 and hMSH2 genes, and tumor samples of five patients were subjected to CGH analysis. A high level of microsatellite instability was associated with histological transformation of two cases of FCL, but no mutations of the hMLH1 and hMSH2 genes were detected in any of the lymphoma samples. In the five cases subjected to CGH analysis, the histological transformation of FCLs was associated with genomic imbalances at 21 chromosomal regions. The genomic abnormalities found were rather heterogeneous and none of the genetic changes were overrepresented in the transformed DLCLs. These data suggest that histological transformation of FCLs to DLCL is frequently associated with genome wide instability at both nucleic acid and chromosomal levels, although mutations of the hMSH1 and hMLH2 genes are not involved in this process.

Original languageEnglish
Pages (from-to)2142-2148
Number of pages7
JournalLeukemia
Volume14
Issue number12
DOIs
Publication statusPublished - Jan 1 2000

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Keywords

  • Follicular lymphoma
  • Genetic instability
  • Lymphoma transformation

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Nagy, M., Balázs, M., Ádám, Z., Petkó, Z., Tímár, B., Szereday, Z., László, T., Warnke, R. A., & Matolcsy, A. (2000). Genetic instability is associated with histological transformation of follicle center lymphoma. Leukemia, 14(12), 2142-2148. https://doi.org/10.1038/sj.leu.2401978