The discovery of viral oncogenes, c-onc, within acutely transforming retroviruses and their cellular homologues, c-onc, has provided a new perspective on the genetic basis of cancer. It is hoped that a complete understanding of the manner in which these genes may be abnormally expressed in the neoplastic cell will make clearer the molecular mechanism of transformation. The proposed research will investigate the postulated role of chromosomal translocations in causing the abnormal structure or expression of cellular oncogenes, We will study v-abl and c-myc oncogenes, whose cellular loci have both been found to be translocated in the human malignancies, chronic myelogenous leukemia and Burkitt's lymphoma, respectively. Fusions will be constructed in vitro between these two genes and the immunoglobulin heavy chain gene. By transfecting the constructs into cloned cell lines, we will attempt to determine the sequences necessary for the tissue-specific expression of these two oncogenes using normal and abnormal promoters. In addition, we will investigate the tissue-specific expression and possible tumorigenicity of these constructs by gene transfer into mice. In the last year of the proposed training period, we will attempt to clone and characterize the c-abl promoter and initiate studies on its functions in the normal cell.
