title: Intronic BCL-6 mutations are preferentially targeted to the translocated allele in t(3;14)(q27;q32) non-Hodgkin B-cell lymphoma.
abstract: Translocations and somatic mutations are common genetic alterations of the BCL-6 gene on chromosome 3q27 in B-cell lymphoma, with implications for lymphomagenesis. The 2 events may have linked origins and can influence juxtaposed loci. To evaluate this further, we compared mutations occurring within the major mutation cluster region of the translocated and untranslocated BCL-6 alleles in 7 t(3;14)(q27;14q32) lymphomas. In 6 of 7 cases, the translocated allele revealed significantly higher mutations (mean, 5.8 x 10-2 bp-1) than did the untranslocated allele (mean, 5.3 x 10-3 bp-1; P <.01). The increase mapped to der(14q32), which retains the BCL-6 promoter and is transcriptionally active, as revealed by fusion transcripts and ongoing somatic mutations, absent in the der(3q27) region. These results indicate that enhanced mutational activity at the translocated allele may be a consequence of loss of cis regulatory elements or gain of IgH enhancer elements. Junctional sequences indicate translocation origins from earlier BCL-6 mutations and switch recombinase events.
authors.affiliation: Department of Haematology, Centre Henri Becquerel, 76000 Rouen, France. fab.jardin@wanadoo.fr
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jardin
authors.forename: Christian
authors.initials: C
authors.lastname: Bastard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Contentin
authors.forename: Francoise
authors.initials: F
authors.lastname: Parmentier
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Picquenot
authors.forename: Herve
authors.initials: H
authors.lastname: Tilly
authors.forename: Freda K
authors.initials: FK
authors.lastname: Stevenson
authors.forename: Surinder S
authors.initials: SS
authors.lastname: Sahota
mesh_terms: D000483:Alleles; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D007438:Introns; D016393:Lymphoma, B-Cell / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors