Small deletions occur in highly conserved regions of the LAZ3/BCL6 major translocation cluster in one case of non-Hodgkin's lymphoma without 3q27 translocation.
This study suggests that BCL6 rearrangement is primarily associated with large cell lymphoma, and that BCL2(-)BCL6(+) NHL could potentially be curable with modern combination chemotherapy.
The gene was identified by fusion to the BCL6/LAZ3 oncogene in an initially described t(3;4)(q27;p11) translocation in a non-Hodgkin's lymphoma cell line.
Because H4 gene expression is tightly coupled to DNA replication, this study suggested an immediate mechanism for deregulated expression of BCL6, leading to the development of non-Hodgkin's lymphoma.
Our results are compatible with previous cytogenetic reports in which the 3q27 translocation was observed in 15-20% of NHL; however, patients with the LAZ3 rearrangements exhibited a wide range of clinico-pathologic characteristics.
BCL6 rearrangements were found in 16/45 (35.5%) DLLC, more frequently in DLCL (15/33, 45%) than in MX-D (1/10, 10%), in 2/31 (6.4%) follicular NHL, and in no other tumor types.
Because the breakpoints involved in these rearrangements are focused in a narrow major translocation cluster (MTC) on chromosome 3, we used genomic probes from this region to study the molecular rearrangements of LAZ3 in a large series of patients (217) with non-Hodgkin's lymphoma (NHL).
These data suggest that chromosomal breakpoints in 3q27 cluster in the proximity of a transcribed gene which represents a candidate protooncogene (bcl-6) involved in B-cell NHL pathogenesis.