Diffuse large B-cell lymphomas (DLBCL) are aggressive tumors that arise from germinal center B-cells (GCB). Post GCB are noted for their heterogeneity and variable clinical outcomes. In previous genome wide studies we found profound alterations in the cytosine methylation patterning of DLBCL and that the expression of activation-induced deaminase (AID) was associated with the loss of methylation in DLBCL patients. AID functions as demethylase during embryonic development, which led us to ask whether AID has demethylase activity during the transit of B-cells through the germinal center, and if over expression contributes to lymphomagenesis through the disruption of DNA methylation.
This question was addressed in an abstract during the 56th annual meeting of the American Society of Hematology (ASH). We studied the epigenetic function of AID in GCB and germinal center-derived lymphomas. Our preliminary results indicate that high AID expression is correlated with a more aggressive phenotype of the disease. We are currently analyzing the epigenetic targets of AID in both normal GCB and tumors, in order to find genes that could be epigenetically deregulated and contribute to the formation of lymphomas. These results demonstrate – for the first time – that AID functions as a demethylase in GCB in vivo. This suggests that the epigenetic role of AID could contribute to lymphomagenesis.