HETEROGENEITY IN B-CELL NEOPLASMS ASSOCIATED WITH REARRANGEMENT OF THE LAZ3 GENE ON CHROMOSOME BAND 3Q27

The LAZ3 gene has been identified on chromosome band 3q27, which is the breakpoint of reciprocal chromosome translocations observed in B-cell non-Hodgkin's lymphoma (NHL). Although the translocations affect various chromosome sites including the immunoglobulin gene loci, molecular studies have indicated that the breakages are clustered within a 10-kb-long major translocation cluster region (MTC) at band 3q27. In the current study, we have used a genomic probe from the MTC to study 51 Japanese patients having B-cell neoplasms with regard to rearrangement of LAZ3. The study detected rearrangement in 12 cases out of 51; the rearrangements occurred within a limited region close to the first exon of the LAZ3 gene. Eight cases out of 12 with rearrangement had diffuse large cell NHL and the immunoblastic variant, including one case transformed from a follicular lymphoma carrying the BCL2 rearrangement. However, the rearrangement was also identified in two NHL patients showing a follicular growth pattern, in one case with indolent chronic lymphocytic leukemia and in one case with high-grade small noncleaved cell lymphoma with a bulky abdominal mass. Cytogenetic analysis revealed t(3;14)(q27;q32) in 2 cases, t(3;22)(q27;q11) in 3, and a newly identified translocation t(3;6)(q27;p21) in one case. LAZ3 expression was demonstrated in cells carrying the LAZ3 rearrangement, suggesting transcriptional deregulation of the gene. Our results are compatible with previous cytogenetic reports in which the 3q27 translocation was observed in 15-20% of NHL; however, patients with the LAW rearrangements exhibited a wide range of clinico-pathologic characteristics. Thus, there is no clear consistent association of the 3q27 translocation with a specific subtype of B-cell neoplasm.