Molecular cloning of a t(11; 14)(q13;q32) translocation breakpoint centromeric to the BCLI‐MTC

In B-cell malignancies, the t(11;14)(q13;q32) at the 11q13 BCLI locus is characterized by a scattering of breakpoint sites along a 100 kb genomic region, between the BCLI major translocation cluster (MTC) and the PRADI (also termed cyclin DI or CCNDI) gene. Recently, the 11q13 breakpoint region was extended on both sides, centromeric to the MTC and telomeric to PRADI. We report here the molecular cloning of a new t(11;14) breakpoint site, 20 kb centromeric to the MTC, from a patient with prolymphocytic leukemia. We subcloned a non-repetitive DNA fragment near the breakpoint and mapped this new 11q13 probe (pHOIIc) relative to already identified breakpoint sites, using long- and short-range physical mapping within the BCLI locus. Rearrangements in the BCLI locus are associated with deregulation of the PRADI gene, which is often overexpressed, particularly in mantle-cell malignancies. The detectable but weak PRADI expression in the case we present suggests that this breakpoint centromeric to the MTC still lies inside the BCLI locus boundaries. We think that attention should be focused on this region centromeric to the BCLI-MTC, where the investigation of previously unidentified translocations may increase understanding of the PRADI gene deregulation in t(11;14) associated pathologies.