Intronic BCL-6 mutations are preferentially targeted to the translocated allele in t(3;14)(q27;q32) non-Hodgkin B-cell lymphoma.
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.
Jardin
Fabrice
F
Department of Haematology, Centre Henri Becquerel, 76000 Rouen, France. fab.jardin@wanadoo.fr
Bastard
Christian
C
Contentin
Nathalie
N
Parmentier
Francoise
F
Picquenot
Jean-Michel
JM
Tilly
Herve
H
Stevenson
Freda K
FK
Sahota
Surinder S
SS
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
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors