A novel bcl-1/JH breakpoint from a patient affected by mantle cell lymphoma extends the major translocation cluster.

Mantle cell lymphoma (MCL) is a B-lymphocytic malignancy frequently associated with the presence of the t(11;14) chromosomal translocation. By using a polymerase chain reaction (PCR) strategy to detect breakpoints within the major translocation cluster (MTC), an unexpectedly large product (about 1.1 kb by using first-round bcl-1/JH primers) has been identified in one out of 16 patients harbouring the t(11;14) translocation. Sequence analysis of the atypical PCR product, re-amplified and cloned with second-round primers, revealed a 459 bp portion corresponding exactly to the 3'-end segment of the MTC, followed by a sequence of 433 bp that lacked homology with any previously known sequence. PCR experiments using DNA from healthy donors identified that fragment as an extension of MTC fused, through a N-region of seven nucleotides, to the JH4 region of IgH gene. A computer-based search of the novel MTC portion aimed at detecting potential recombination motifs revealed the presence of several 4-bp sequences (5'-CCAG-3' or its complement 5'-CTGG-3'), one of them within seven nucleotides from the putative breakpoint, known to play a role in non-homologous recombination events at the Ig loci. The recognition of this novel breakpoint may have important implications for the diagnosis and detection of minimal residual disease in t(11;14)-positive lymphomas. Copyright 2002 John Wiley & Sons, Ltd.