TUMOR-ASSOCIATED DNA MOVEMENT

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Increasing evidence suggests that oncogenesis may require specific genetic events, some of which may involve chromosomal translocations. We have found that, in many murine B-cell tumors, a segment of DNA is frequently translocated (tumor-associated recombining DNA or tar DNA). In two B-cell lines, tar DNA has recombined downstream from potentially active immunoglobulin gene promoters. Recombinations involving tar DNA are not related to c-myc gene translocations also seen in many B-cell tumors. Tar DNA recombinations are found much more frequently in lambda-producing B-cell lines than in kappa-producing tumors. It may be that tar recombination is a developmentally regulated event during B-cell maturation. We will investigate tar DNA recombination to elucidate the molecular mechanisms underlying chromosomal recombinations in B-cell tumors and to determine if these recombinations are important for tumorigenesis. DNA movement may play a significant role in the transformation process as well as in normal development and evolution. (D)