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)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA036370-02
Application #
3173934
Study Section
Molecular Biology Study Section (MBY)
Project Start
1983-12-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Brandeis University
Department
Type
Schools of Arts and Sciences
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
Daitch, L E; Moore, M W; Persiani, D M et al. (1992) Transcription and recombination of the murine RS element. J Immunol 149:832-40
Persiani, D M; Selsing, E (1989) DNase I sensitivity of immunoglobulin light chain genes in Abelson murine leukemia virus transformed pre-B cell lines. Nucleic Acids Res 17:5339-48
Siminovitch, K A; Moore, M W; Durdik, J et al. (1987) The human kappa deleting element and the mouse recombining segment share DNA sequence homology. Nucleic Acids Res 15:2699-705
Persiani, D M; Durdik, J; Selsing, E (1987) Active lambda and kappa antibody gene rearrangement in Abelson murine leukemia virus-transformed pre-B cell lines. J Exp Med 165:1655-74
Ju, S T; Selsing, E; Huang, M C et al. (1986) Genetic analysis of low lambda 1 chain production in mice. J Immunol 136:2684-8
Moore, M W; Durdik, J; Persiani, D M et al. (1985) Deletions of kappa chain constant region genes in mouse lambda chain-producing B cells involve intrachromosomal DNA recombinations similar to V-J joining. Proc Natl Acad Sci U S A 82:6211-5