Splenic Lymphoma With Villous Lymphocytes: Analysis of BCL-1 Rearrangements and Expression of the Cyclin Dl Gene

Abstract

The translocation t(11;14)(q13;q32) occurs in about 15% of patients with splenic lymphoma with villous lymphocytes (SLVL) or the closely related disorder lymphoplasmacytic lymphoma (LPL). To characterize the nature and frequency of rearrangements of the BCL-1 locus in SLVL/LPL and to document the effect of these genetic alterations on the expression of the cyclin D1 gene, we analyzed 22 cases of SLVL/LPL with defined cytogenetic abnormalities by both conventional electrophoresis (CE) and pulse-field gel electrophoresis (PFGE) and by Northern blotting. Four SLVL/LPL cases showed rearrangement of the BCL-1 locus. In two cases with t(11;14)(q13;q32), different breakpoints were identified; one mapped adjacent to the major translocation cluster (MTC) and the other within a 28-kb region telomeric of it. In a third case of SLVL with no cytogenetic abnormality of 11q13, a novel breakpoint approximately 100 kb centromeric of MTC was detected by PFGE. The fourth case, which had a normal karyotype, demonstrated rearrangement with a BCL-1 probe immediately telomeric of MTC. This case may have had a small deletion of 0.5 kb from within the BCL-1 locus. No rearrangement of the BCL-1 locus or within the cyclin D1 gene was detected by CE or PFGE in any of the remaining 18 SLVL/LPL samples. Northern blot analysis showed expression of a normal-sized cyclin D1 transcript in the two SLVL/LPL cases with t(11;14)(q13;q32). In cases that lacked a cytogenetically demonstrable t(11;14) translocation, no cyclin D1 transcript was detected. Analysis of the BCL-1 locus was also performed in three other cases of B-cell disorders with t(11;14)(q13;q32) detected cytogenetically. Two cases were analyzed by Southern blot and showed rearrangement of the BCL-1 locus. Expression of high-level normal-sized and/or truncated cyclin D1 transcript was also detected in these cases. These data show the importance of PFGE in the detection of rearrangements in the BCL-1 locus and show further the complexity of rearrangements in this locus.