Generation of a Variant T(2;8) Translocation of Burkitt's Lymphoma by Site-Specific Recombination via the Kappa Light-Chain Joining Signals

Abstract

We analyzed the Burkitt's lymphoma line BL64 in which a reciprocal translocation joins the immunoglobulin kappa light-chain locus on chromosome 2 to the c-myc gene on chromosome 8. The breakpoints on the two marker chromosomes 8⁺ and 2p^- occurred 5′ of the J₅ segment within the conserved nonamer and heptamer recombination sequences. Both signals were detected directly adjacent to the breakpoints in sequences of chromosome 8 suggesting that the translocation in BL64 was catalyzed by enzymes normally involved in V-J recombination. The distance between the c-myc gene and the breakpoint in J_k kappa amounts to at least 90 kilobases on the DNA level. In one allele of the c-myc gene somatic mutations were found in the promoter-leader region. This allele is transcribed and is supposed to be involved in the translocation. The half-life of the c-myc-specific mRNA in BL64 cells is not prolonged in comparison to the normal c-myc message. These results suggest that in Burkitt's lymphoma the translocation occurs during an early stage of B-cell differentiation and that in the variant translocations mechanisms other than a prolonged half-life, such as changes in transcriptional rates, or other posttranscriptional RNA processing contribute to the high steady-state level of c-myc RNA in the cytoplasm.