Clonal history of a human follicular lymphoma as revealed in the immunoglobulin variable region genes.

The variable region genes used to encode the immunoglobulin expressed by tumour cells of a patient with follicular lymphoma have been identified and sequenced. Initially, a lymph node biopsy was analysed and revealed usage of VH and V kappa genes which had numerous substitutions as compared with the closest germ line genes. The pattern of mutations in VH was consistent with a role for positive selection by antigen. In addition, there was evidence in both VH and V kappa sequences for clonal heterogeneity. After 5 years, which included treatment with chemotherapy, the patient relapsed with tumour cells present in the blood. Analysis of the V-genes used by the emerging tumour revealed a single homogeneous sequence for both VH and VL, which, in each case, matched closely one of the sequences in the original lymph node biopsy. These results indicate that selection, possibly mediated by antigen, can operate on a cell destined to give rise to lymphoma, and that intraclonal variation can occur after the neoplastic event. However, in this case, late relapse in the blood is dominated by a single clone.