ANALYSIS OF V-H GENES USED BY NEOPLASTIC B-CELLS IN ENDEMIC BURKITTS-LYMPHOMA SHOWS SOMATIC HYPERMUTATION AND INTRACLONAL HETEROGENEITY

Tumor cell lines from six typical cases of endemic Epstein-Barr virus (EBV) genome-positive Burkitt's lymphoma (BL) have been investigated for usage and mutational pattern of Ig V-H genes. The neoplastic cells all had a t(8;14) (q24;q32) translocation involving the c-myc protooncogene, The V-H genes were derived from V(H)1, V(H)3 and V(H)4, and both the IgM-positive (four cases) and IgG-positive (two cases) were extensively mutated from germline sequence. In two cases, early and late passage tumor cells were available, and the V-H nucleotide sequences were identical, indicating that mutations had not accumulated in vitro. In a further case, there was evidence of sequence heterogeneity, which appeared to have been generated in vivo, indicating that the tumor cell V-H gene was able to undergo posttranslocation somatic hypermutation. Analysis of the relatively nonpolymorphic V(H)4 genes for the pattern of replacement or silent mutations did not show a role for antigen selection in the expressed sequences. (C) 1995 by The American Society of Hematology.