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Genetics Department, Medicine Branch, National Cancer Institute, Bethesda, Maryland 20889 [F. L., V. B., I. R. K.]; Centro Studi e Ricerche della Sanitá dell'Esercito, 00184 Roma, Italy [F. L.]; and Hospital for Sick Children Research Institute and Department of Immunology, University of Toronto, Toronto, Ontario, M5G 1X8, Canada [C. J. G., J. S. D.]
Pilot studies in human populations have demonstrated a correlation between the level of antigen receptor trans-rearrangements and risk (at the population level) of lymphoid malignancy. Irradiation of newborn severe combined immune deficiency mice results in an increased risk of subsequent development of thymic lymphoma (100% of mice so irradiated are dead of thymic lymphoma by 20 weeks of age). We, therefore, assayed the occurrence of trans-rearrangements in this well-controlled mouse mutant system and found a 50–100-fold increase in the absolute number of TCRGV-TCRBJ trans-rearrangements compared to unirradiated littermates (and a comparable fold increase over age-matched BALB/c mice) at 2 weeks following irradiation. We also found a marked disproportion in generating trans-rearrangements versus intralocus rearrangements in the severe combined immune deficiency system compared to BALB/c, independent of irradiation. The trans-rearrangements noted were polyclonal in nature. These data, again, suggest that the absolute level of antigen receptor trans-rearrangements may serve as a biomarker of lymphoma risk.
1 To whom requests for reprints should be addressed, at Naval Hospital, Building 8, Room 5101, Bethesda, MD 20889. Phone: (301) 496-0909; Fax: (301) 496-0047; E-mail: kirsch@helix.nih.gov.
Received 4/28/97. Accepted 8/ 1/97.
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