Translocations involving 3q27 that affect the BCL6 gene are common and specific chromosomal abnormalities in B-cell precursor non-Hodgkin lymphoma (mainly diffuse large-cell and follicular lymphoma), but they have not been reported in Burkitt lymphoma.
In addition, two other genes, BCL6 and BCL2, which are classically related to apoptosis and non-Hodgkin lymphoma, were shown for the first time to be involved in amplification.
Chromosomal translocation affecting the 3q27 band, where the BCL6 gene is localized, is one of the most common genetic abnormalities in non-Hodgkin's lymphoma of B-cell type (B-NHL).
In B cell lymphomas, structural alterations of the BCL-6 promoter region, including chromosome translocation and somatic hypermutation, represent the most frequent genetic lesions associated with non-Hodgkin lymphoma, especially of diffuse large cell lymphoma, a malignancy often derived from germinal centre (GC) B cells.
Translocations of the BCL-6 gene to heterologous promoters and mutations of its 5'-noncoding regulatory region were reported to be potential mechanisms for deregulating BCL-6 expression and for playing a role in the genesis of non-Hodgkin lymphoma.
Mutation analysis of the 5' noncoding regulatory region of the BCL-6 gene in non-Hodgkin lymphoma: evidence for recurrent mutations and intraclonal heterogeneity.
In order to elucidate the molecular mechanism(s) for BCL6 translocation, we identified translocational partner genes by subjecting clinical biopsy samples from patients with non-Hodgkin's lymphoma to 5'-rapid amplification of cDNA ends (5'-RACE).
The t(2;3)(q21;q27) translocation in non-Hodgkin's lymphoma displays BCL6 mutations in the 5' regulatory region and chromosomal breakpoints distant from the gene.
Chromosomal translocations and/or their molecular equivalents involving the BCL6 gene on 3q27 band have been suggested to be involved in the development of non-Hodgkin's lymphoma of B-cell type (B-NHL).
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.
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.
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.