Variant translocations in sporadic Burkitt's lymphoma detected in fresh tumour material: analysis of three cases.

Burkitt's lymphoma/Burkitt cell leukaemia (BL) is characterized by one of the reciprocal translocations involving the MYC oncogene on chromosome 8 and one of the immunoglobulin (Ig) loci on chromosomes 14, 2 or 22. In the few cell lines with the variant translocations t(2;8) and t(8;22) reported to date, the breakpoints on chromosome 8 were located downstream of MYC at a distance of up to 300 kb and more. Here, we describe three new cases with variant translocations. Fresh tumour material from paediatric patients, negative for the common translocation t(8;14), was analysed using a long-distance (LD) polymerase chain reaction (PCR) approach. On chromosome 8, primers were derived from several different regions 3' of MYC, and on chromosomes 2 and 22 from the constant regions of the Ig kappa (Igkappa) and lambda (Iglambda) genes. One translocation t(2;8) and two t(8;22) were detected. In the t(2;8) translocation, the chromosome 8 breakpoint was located 2 kb 3' of the MYC exon 3 and the chromosome 2 breakpoint within an unrearranged Igkappa locus. The breakpoints of the two translocations t(8;22) were detected 16 kb for one and 58 kb for the other downstream of MYC. Sequencing the t(8;22) translocation in one of the cases showed hypermutation of the translocated variable Vlambda4b gene. The presence of hypermutated variable regions in the t(8;22) case suggests germinal centre B cells as the origin of this translocation. The t(2;8) translocation is the first description of a translocation t(2;8) involving an unrearranged Igkappa gene. A mechanism different from V-J recombination and somatic hypermutation has to be proposed for this translocation.