Trans-rearrangements and the risk of lymphoid malignancy

Abstract

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. 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. 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. 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-rearrangement is, at least in part, responsible for the majority of presumably 'malevolent' translocations associated with the transformation of lymphocytes.