title: Heterogeneity of BCL6 rearrangements in nodular lymphocyte predominant Hodgkin's lymphoma.
abstract: OBJECTIVE
  Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) showed recurrent rearrangement of the BCL6 which is gene detected in 48% of cases analyzed by interphase-fluorescent in situ hybridization (FISH). These findings point to a critical role for BCL6 in the development of this distinct Hodgkin's lymphoma. We present our results of metaphase-FISH analyses aimed at identifying and characterizing BCL6-related chromosomal translocations in NLPHL.
  
  
  METHODS
  Four NLPHL cases with available metaphase spreads obtained either at the time of diagnosis or during progression to diffuse large B-cell lymphoma (DLBCL) were collected. Extensive metaphase-FISH analysis was performed to identify the affected partner chromosomes and reciprocal breakpoints.
  
  
  RESULTS
  Each of the analyzed NLPHL cases showed a different type of BCL6 rearrangement that included the t(3;22)(q27;q11) targeting immunoglobulin (IG) alpha chain locus, complex t(3;7;3;1) involving the 7p12/Ikaros gene region, t(3;9)(q27;p13) affecting an unknown gene in vicinity of PAX5, and t(3;4)(q27;q32) showing the alternative 3q27 breakpoint outside BCL6 and possibly, an internal deletion of BCL6. Retrospective interphase-FISH analysis of 2 cases with subsequent DLBCL showed the same type of BCL6 translocation as in NLPHL samples.
  
  
  CONCLUSIONS
  The spectrum of BCL6 aberrations targeting IG as well as non-IG loci in NLPHL is similar to that found in DLBCL. These findings further support the hypothesis of a germinal center B-cell-derived origin of NLPHL and of a relationship between these two lymphoma entities. This latter issue is additionally illustrated in two NLPHL patients who subsequently developed DLBCL and showed the same type of BCL6 rearrangements in both tumors.
authors.affiliation: Center for Human Genetics, Katholieke Universiteit Leuven, Belgium.
authors.forename: Iwona
authors.initials: I
authors.lastname: Wlodarska
authors.forename: Michel
authors.initials: M
authors.lastname: Stul
authors.forename: Chris
authors.initials: C
authors.lastname: De Wolf-Peeters
authors.forename: Anne
authors.initials: A
authors.lastname: Hagemeijer
mesh_terms: D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors