Acquired somatic mutations in non-coding region of bcl-6 gene in germinal center-type diffuse large B-cell lymphoma

Abstract

To investigate the mutation of 5' non-coding region of bcl-6 gene in germinal center B-cell (GCB) subtype of diffuse large B-cell lymphoma (DLBCL). t(14;18) detection and immunohistochemical staining (EnVision method) were performed in 60 cases of DLBCL, which were divided into GCB and non-GCB subtypes. Polymerase chain reaction (PCR), single-strand conformation polymorphism and direct DNA sequencing were used to identify mutations in the 5' non-coding region of the bcl-6 gene. Seven of 60 cases showed t(14;18) translocation in the major breakpoint region. Using minimally acceptable criteria, 18 of 60 cases were probably to be germinal centre derived. Bcl-6 mutations were detected in 12 of 60 cases (20.0%) of DLBCL, with a significantly higher frequency in the GCB subgroups (7/18) than in the non-GCB subgroups (11.9%, 5/42). Bcl-6 mutations occurred most frequently in +363 and +469 sites. An association of bcl-6 mutation and GCB subgroup was obtained. The 5' regulatory region of the bcl-6 gene underwent less frequent somatic hypermutation during lymphomagenesis than the results of previous reports. Bcl-6 mutation occurred mostly in the GCB subtype and detection of t(14;18) seems helpful in the classification of DLBCL.