Structural alterations and expression of immunoglobulin (Ig), T-cell receptor (TCR) and various growth affecting genes are studies in normal, """"""""premalignant,"""""""" and malignant tumors and cell lines. A. We have shown that hybrid genes are formed by site specific recombination between variable segments from one immune receptor locus and joining segments from another. We have demonstrated that such events occur in the peripheral T-cells of all normal individuals but are 100 times more frequent in the peripheral Tells of patients with ataxia-telangiectasia (AT). These hybrid genes l) affect and alter the repertoire of immune receptor diversity, 2) suggest that an underlying defect in AT may be chromatin """"""""hyperaccessibility,"""""""" and 3) provide a possible screening test for people at an increased risk for the development of lymphoid specific chromosomal translocations, and therefore lymphoid malignancy. We have completed a pilot study of individuals involved in the agriculture industry in which we have demonstrated an acquired transient """"""""AT-like"""""""" picture in individuals exposed to a variety of pesticides and herbicides. These individuals are the same population for which epidemiological studies have suggested an increased risk of leukemia and lymphoma. B. We have developed a murine model of lymphocyte-specific genetic instability and demonstrated its utility as a predictor of cancer risk as a result of certain inherited genes or acquired exposures or both.
