A comprehensive genetic and histopathologic analysis identifies two subgroups of B-cell malignancies carrying a t(14;19)(q32;q13) or variant BCL3-translocation

Leukemia. 2007 Jul;21(7):1532-44. doi: 10.1038/sj.leu.2404695. Epub 2007 May 10.

Abstract

The biologic and pathologic features of B-cell malignancies bearing a translocation t(14;19)(q32;q13) leading to a fusion of IGH and BCL3 are still poorly described. Herein we report the results of a comprehensive cytogenetic, fluorescence in situ hybridization (FISH), molecular and histopathological survey of a large series of B-cell malignancies with t(14;19) or variant translocations. A total of 56 B-cell malignancies with a FISH-proven BCL3 involvement were identified with the translocation partners being IGH (n=51), IGL (n=2), IGK (n=2) and a non-IG locus (n=1). Hierarchical clustering of chromosomal changes associated with the t(14;19) indicated the presence of two different groups of IG/BCL3-positive lymphatic neoplasias. The first group included 26 B-cell malignancies of various histologic subtypes containing a relatively high number of chromosomal changes and mostly mutated IgVH genes. This cluster displayed three cytogenetic branches, one with rearrangements in 7q, another with deletions in 17p and a third one with rearrangements in 1q and deletions in 6q and 13q. The second group included 19 cases, mostly diagnosed as B-cell chronic lymphocytic leukemia (B-CLL), and characterized by few additional chromosomal changes (e.g. trisomy 12) and unmutated IgVH genes. In conclusion, our study indicates that BCL3 translocations are not restricted to B-CLL but present in a heterogeneous group of B-cell malignancies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B-Cell Lymphoma 3 Protein
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 19
  • Cytogenetic Analysis
  • Female
  • Gene Rearrangement
  • Genes, Immunoglobulin
  • Histocytochemistry
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, B-Cell / classification
  • Leukemia, B-Cell / genetics*
  • Leukemia, B-Cell / pathology
  • Lymphoma, B-Cell / classification
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / pathology
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins / genetics*
  • Transcription Factors / genetics*
  • Translocation, Genetic*

Substances

  • B-Cell Lymphoma 3 Protein
  • BCL3 protein, human
  • Proto-Oncogene Proteins
  • Transcription Factors