V(H) and V(L) gene analysis in sporadic Burkitt's lymphoma shows somatic hypermutation, intraclonal heterogeneity, and a role for antigen selection

Abstract

Tumor cell lines and one tumor biopsy from seven cases of Epstein-Barr virus (EBV) genome-negative sporadic Burkitt's lymphoma (BL) have been investigated for usage and mutational pattern of Ig variable region genes. The V(H) genes were derived from the V(H) 3 (one) and V(H)4 (six) families and both the IgM-positive (six) and the IgA-positive (one) were all mutated from their germline counterparts. The V(L) genes were derived from Vκ1 (one), Vκ3 (one), Vλ1 (four), and Vλ2 (one) families and were also somatically hypermutated. Biopsy material from one of the IgM-positive cases showed V(H) and V(L) sequences that matched the derived cell line, with additional intraclonal sequence heterogeneity, indicating that the tumor cells had undergone posttranformation somatic mutation. Mutational patterns in V(H) genes did not show a conventional role for antigen in selecting tumor cell sequences. In contrast, patterns in V(L) sequences were consistent with a role for antigen in five of seven cases. The pattern of extensive scattered somatic hypermutation and intraclonal variation is similar to that in V(H) sequences of EBV genome-positive endemic BL, although the degree of mutational activity is less. These common features indicate that B cells involved in the two variants of BL may share a common clonal history.