To the Editor: We read with interest the report of Chibbar et al. (1) describing the molecular analysis of bcl-1 rearrangement in mantle cell lymphoma (MCL). These authors demonstrated major translocation cluster rearrangements in 30 to 40% of MCL, as in previous reports, but were unable to show p94PS rearrangement as we and others have previously reported (2, 3, 4, 5). They described an apparent HindIII polymorphism at the p94PS locus but failed to identify rearrangements with BamHI, EcoRI, or HindIII restriction analysis.

Using a 460 bp PvuII-SmaI genomic p94PS probe (provided by Dr. Timothy Meeker, University of Kentucky, Lexington), we identified rearrangements on Southern blot in 10 of 53 MCL (19%). Each rearrangement was confirmed on two or more restriction digests other than HindIII; no case was interpreted as having a p94PS rearrangement based solely on nongermline HindIII bands (Table 1). Six cases were further verified by rehybridization of EcoRI blots with the 2 kb genomic q13–7 translocation breakpoint probe, which lies approximately 4 kb downstream (telomeric) of the p94PS breakpoint (6) (provided by Dr. Dalal Jadayel, Institute of Cancer Research, Sutton, UK). Seven of the 10 p94PS or q13–7 rearrangements showed comigration with a rearranged immunoglobulin heavy chain joining gene band consistent with the t(11;14)(q13;q32). Given that Chibbar et al. (1) used BamHI and EcoRI digests in their study and that all p94PS rearrangements in our series were present on one or both of these digests, it is unclear why they were unable to detect rearrangements at this locus.

TABLE 1 Chromosome 11q13 p94PS and q13-7 Rearrangements in Mantle Cell Lymphoma
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Review of HindIII-digested DNA from cases of mantle cell and other non-Hodgkin's lymphomas shows an ∼2.8 kb p94PS germline band, plus the ∼3.8 kb nongermline band described by Chibbar et al. in approximately 15% of cases. The nongermline band in virtually all cases was faint relative to the germline band, more consistent with a pseudogene or restriction digest artifact rather than a true polymorphism.

Multiple 11q13 translocation breakpoints have been described in MCL within the approximately 120 kb span centromeric of the CCND1/cyclin D1 gene by fluorescence in situ hybridization and Southern blot analysis, as well as additional breakpoints outside this span identified by fluorescence in situ hybridization techniques (7, 8). Unfortunately, as noted by Chibbar et al. (1), these breakpoints are somewhat scattered at each locus and difficult to identify by polymerase chain reaction with the exception of the tight clustering at the major translocation cluster (11). The 11q13 translocations, including those at p94PS, almost uniformly lead to overexpression of cyclin D1 at both the mRNA and protein levels (9, 10). Such expression can be of diagnostic value in separating MCL from other non-Hodgkin's lymphomas.