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 t he 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 d istance of up to 300 kb and more. Here, we describe three new cases with va riant translocations. Fresh tumour material from paediatric patients, negat ive for the common translocation t(8;14), was analysed using a long-distanc e (LD) polymerase chain reaction (PCR) approach. On chromosome 8, primers w ere derived from several different regions 3' of MYC, and on chromosomes 2 and 22 from the constant regions of the Ig kappa (Ig kappa) and lambda (Ig lambda) genes. One translocation t(2;8) and two t(8;22) were detected. In t he t(2;8) translocation, the chromosome 8 breakpoint was located 2 Bb 3' of the MYC exon 3 and the chromosome 2 breakpoint within an unrearranged Ig k appa locus. The break-points of the two translocations t(8;22) were detecte d 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 transl ocated variable V lambda 4b gene. The presence of hypermutated variable reg ions 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 Ig kappa gene. A mechanism d ifferent from V-J recombination and somatic hypermutation has to be propose d for this translocation.