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 i s characterized by a scattering of breakpoint sites along a 100 kb gen omic region, between the BCL1 major translocation cluster (MTC) and th e PRAD1 (also termed cyclin D1 or CCND1) gene. Recently, the 11q13 bre akpoint 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 wit h prolymphocytic leukemia. We subcloned a non-repetitive DNA fragment near the breakpoint and mapped this new 11q13 probe (pHO11(c)) relativ e to already identified breakpoint sites, using long- and short-range physical mapping within the BCL1 locus. Rearrangements in the BCL1 loc us are associated with deregulation of the PRAD1 gene, which is often overexpressed, particularly in mantle-cell malignancies. The detectabl e but weak PRAD1 expression in the case we present suggests that this breakpoint centromeric to the MTC still lies inside the BCL1 locus bou ndaries. We think that attention should be focused on this region cent romeric to the BCL1-MTC, where the investigation of previously unident ified translocations may increase understanding of the PRAD1 gene dere gulation in t( 11;14) associated pathologies. (C) 1994 Wiley-Liss, Inc .