New type of t(14; 18) in a non-Hodgkin's lymphoma provides insight in molecular events in early B-cell differentiation

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Abstract
In this report a follicular non-Hodgkin's lymphoma (NHL) carrying an unusual t(14;18) is described. This translocation most likely occurred during the VH to D-JH rearrangement process of the IgH locus. From the data combined with data from the literature we conclude that the chance for development of a t(14;18) decreases during progression of the immunoglobulin rearrangement process in the pre-B-cell ontogeny. This is probably due to decreased accessibility of the bcl-2 locus by reduced transcription. We analysed the somatic mutation pattern of the productively rearranged IgH gene. Like other follicular lymphomas, somatic mutations were present in this gene and indicated positive selection, probably for an antigen. We found no evidence for ongoing induction of somatic mutations during lymphoma development. We conclude that bcl-2 gene deregulation, but not the precise moment at which this occurs during the pre-B-cell stage, influences the development of follicular NHL.