The pattern of BCL-6 gene hypermutations in diffuse large B-cell lymphoma of nodal and extranodal origin

Abstract

INTRODUCTION: Rearrangement and hypermutations of the bcl-6 oncogene are found commonly in diffuse large B-cell lymphoma (DLBCL), suggesting a pathogenetic role. METHODS: The pattern of bcl-6 gene hypermutations was studied in 101 Hong Kong Chinese patients with nodal or extranodal DLBCL. The technique used was polymerase chain reaction, denaturing gradient gel electrophoresis and direct DNA sequencing. RESULTS: The primary sites of the tumors involved lymph nodes in 52 cases, stomach in 32 and other extranodal sites in 17. Hypermutations at the E1.11 and/or El.12 sites of bcl-6 gene were detectable in 54% of the primary nodal and 84% of extranodal DLBCL (p < 0.001). DNA sequencing of the PCR fragments revealed that the G2096C of the E1.11 segment of the bcl-6 gene was the most commonly mutation observed in DLBCL of either nodal (18%) or extranodal (38%) origin. Other random mutations found included G2097A, T2123A and C2145T. CONCLUSIONS: We concluded that a significantly higher frequency of bcl-6 gene hypermutations was found in diffuse large B-cell lymphoma of primary extranodal origin, including those arising from the stomach, than that of the nodal counterparts. However, the pattern of mutations was similar for the two groups. This suggests that, although a common genetic mechanism is involved, bcl-6 gene hypermutations appears to play a more important role during the pathogenesis of primary extra-nodal lymphoma of diffuse large B-cell histology