Deregulation of FCGR2B expression by 1q21 rearrangements in follicular lymphomas

We report here the molecular cloning and characterization of a t(1;14)(q21; q32) in a follicular lymphoma (FL) with an unusual BCL2 aberration. Fluores cence in situ hybridization (FISH) and Southern blot analysis of tumor cell s identified the translocation breakpoint within the 5' switch region of IG HG (S gamma). We cloned the chimeric breakpoint region approximately 1.5 kb p downstream from the HindIII site of 5'S gamma2 on chromosome 14q32 and id entified a 360-bp novel segment with homology to the CpG island clone 11h8. Two BAC clones containing this sequence were isolated and mapped to 1q21 b y FISH. BAC 342/P13 contained sequences homologous to Fc gamma receptors 2A , 3A, 2B, 3B, and a heat shock protein gene HSP70B. The translocation broug ht the S gamma2 region of a productive IGH allele 20 similar to 30 kbp upst ream of FCGR2B. As a result of the translocation, the b2 isoform of FCGR2B was overexpressed in the tumor. Screening of a panel of 76 B-cell lymphomas with 1q21-23 cytogenetic aberrations by Southern blot analysis using break point probes identified an additional FL with a t(14;18)(q32;q21) and a bre akpoint in the FCGR2B region. These results suggest that FCGR2B may be dere gulated by 1q21 aberration in BCL2 rearranged FLs and possibly play a role in their progression.