THE ORGANIZATION OF THE BCL6 GENE

The chromosomal translocation involving 3q27 has been recently describ ed in B-cell malignancies, especially in diffuse large cell lymphomas. We have previously cloned the breakpoint cluster region of 3q27 desig nated as the BCL6 locus, pre viously known as BCL5, and subsequently c loned the cDNA for the BCL6 (we previously reported it as BCL5) gene e ncoding a novel Cys2-His2 zinc-finger protein, which locates adjacent to the breakpoints and is activated through the translocation. To eluc idate whether rearrangements occur within the BCL6 gene, we characteri zed the genomic structure of the gene. The BCL6 gene encompasses about 26 kilobases (kb) and consists of nine exons. Translation start site is located in exon 3 and zinc-finger motif is distributed in the exons 6 to 9. We have identified at least two types of mRNA alternatively s pliced, which contain or do not contain exon 2 of 134 bp coding for th e 5' untranslated region. A large intron 1 of 9 kb is not efficiently spliced out, which might result in the creation of minor 10-12-kb tran scripts observed in the Northern blot analysis in addition to major 3. 8-kb transcripts. The breakpoints are clustered around the first exon, and the putative regulatory region of the BCL6 gene is removed throug h the translocation, leading to the overexpression of the gene.