Trans-rearrangements and the risk of lymphoid malignancy

Background: Antigen receptor 'trans-rearrangements' occur in all individuals and represent a particular type of genetic instability whose mechanism, V(D)J recombination, is the same as that required for the development of a normal immune response. Design: We have measured the level of trans-rearrangements in a variety of populations characterized by increased risk for the development of lymphoid malignancy. The human populations studied include those with an inherited predisposition to lymphomagenesis (ataxia-telangiectasia patients), as well as populations at increased risk because of an occupational (agriculture workers) or iatrogenic (Hodgkin's disease patients) exposure. In addition, we have developed a mouse model for the more controlled analysis of these events. Results: There is a correlation between the absolute number of trans-rearrangements (as a population mean or median) and risk of lymphoma, whether that risk is based on an inherited predisposition or acquired exposure. Conclusion: This assay may serve as an easily measurable biomarker of lymphoma risk. If so, it is more than a fortuitous biomarker since the same mechanism responsible for the formation of trans-rearrangements is, at least in part, responsible for the majority of presumably 'malevolent' translocations associated with the transformation of lymphocytes.