Expression of the recombination activating genes (RAG1 and RAG2) is not detectable in Epstein-Barr virus-associated human lymphomas

The expression of the recombination activating genes (RAG1 and RAG2) is lar gely restricted to immature lymphoid cells. Previous studies have suggested that Epstein-Barr virus (EBV) infection may lead to a re-induction of RAG expression in mature B lymphocytes. To assess the significance of this mech anism for the pathogenesis of malignant lymphomas, we have examined the exp ression of RAG genes in I I cases of EBV-associated endemic Burkitt's lymph oma (BL), 25 cases of Hodgkin's disease (HD, 17 EBV+, 8 EBV-) and 10 cases of follicular non-Hodgkin's lymphoma (NHL). Using in situ hybridization, ex pression of the RAGs was detected in cortical thymocytes in normal thymus a nd in the tumor cells of 2 of 3 lymphoblastic NHL, By contrast, there was n o detectable RAG expression in the BL, HD and follicular NHL cases, Our res ults indicate that re-induction of RAG expression does not occur in human l ymphomas in vivo. Thus, it is unlikely to play a role in the development of translocations involving immunoglobulin gene loci which are characteristic ally found in BL and follicular NHL, Moreover, our study shows that in situ hybridization is a suitable method for the analysis of RAG expression in h uman tissue sections. (C) 2001 Wiley-Liss, Inc.