MOLECULAR-CLONING OF A T(11-14)(Q13-Q32) TRANSLOCATION BREAKPOINT CENTROMERIC TO THE BCL1-MTC

In B-cell malignancies, the (11;14)(q13;q32) at the 11q13 BCL1 locus is characterized by a scattering of breakpoint sites along a 100 kb genomic region, between the BCL1 major translocation cluster (MTC) and the PRAD1 (also termed cyclin D1 or CCND1) gene. Recently, the 11q13 breakpoint region was extended on both sides, centromeric to the MTC and telomeric to PRAD1. 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 (pHO11(c)) relative to already identified breakpoint sites, using long- and short-range physical mapping within the BCL1 locus. Rearrangements in the BCL1 locus are associated with deregulation of the PRAD1 gene, which is often overexpressed, particularly in mantle-cell malignancies. The detectable but weak PRAD1 expression in the case we present suggests that this breakpoint centromeric to the MTC still lies inside the BCL1 locus boundaries. We think that attention should be focused on this region centromeric to the BCL1-MTC, where the investigation of previously unidentified translocations may increase understanding of the PRAD1 gene deregulation in t( 11;14) associated pathologies. (C) 1994 Wiley-Liss, Inc.