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Staging of T-Cell Receptor ß Chain Gene Rearrangements and ras Oncogene Mutations in the Development of Murine Thymic Lymphomas¹

Department of Pathology, Kaplan Cancer Center, New York University, New York, New York 10016

While it is known that the T-cell receptor ß chain gene is rearranged in fully developed murine thymic lymphomas induced by N-nitrosomethylurea and that the ras gene is activated in approximately 50% of these tumors (L. E. Diamond et al., Mol. Cell. Biol., 8: 2233–2236, 1988), it is unknown when these events occur or where the cells committed to a malignant phenotype are first located. We have studied these questions by treating mice with N-nitrosomethylurea, extracting thymocytes and bone marrow cells from the treated mice before they would have developed tumors, transferring the cells into recipient mice, monitoring those mice until they developed lymphoid tumors, and analyzing those tumors. This analysis showed that the initial cells committed to becoming malignant can be located in either the bone marrow or thymus and that both activation of the ras oncogene and rearrangements of the T-cell receptor gene can occur earlier than 30 days after N-nitrosomethylurea treatments. Furthermore, these results suggest that the T-cell receptor ß chain gene can undergo additional rearrangements during progression of a tumor.

¹ This investigation was supported by NIH Grants CA36327 and CA16239 and by USPHS Training Grant 5 T32 GM07308 from the National Institute of General Medical Sciences. A. P. is a scholar of the Leukemia Society of America.

² Present address: Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104.

³ To whom requests for reprints should be addressed, at Department of Pathology, New York University Medical Center, 550 First Ave., New York, NY 10016.

Received 8/16/90. Accepted 1/ 3/91.

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