Burkitt lymphoma is a malignant lymphoma associated with characteristic chromosomal translocations between the c-myc oncogne and one of the three immunoglobulin gene loci.
The aim of this project is to investigate the contribution of these somatic rearrangements to the process of malignant transformation. By analyzing the role of c-myc in the development of a malignant phenotype in an in vitro cell system, one may help to elucidate the role of the oncogene in the in vivo development of hematologic milignancy. Introduction of oncogenes into cultured rat embryo fibroblasts has been shown to induce a malignant phenotype in those cells. In the proposed project, these techniques will be extended to lymphocytes, the cells known to be targets in vivio for malignant change associated with myc rearrangements. The myc gene, in its normal and rearranged forms, will be introduced into normal mouse spleen lymphocytes via the process of DNA-mediated gene transfer. Malignant transformation will be assayed in vitro by assessment of characteristic changes in growth requirements (decreased need for fetal calf serum supplementation, growth in soft agar, loss of requirement for B-cell growth factors), and in vivo by the formation of tumors when injected into irradiated nude mice. Resultant changes will be correlated with alterations in c-myc expression at the transcriptional and translational level. Transcription will be assayed by Sl analysis of mRNA species. Protein production may be assessed by antibody analysis or by fusion of the myc promoters to the structural gene of a more easily detected protein.
