Chromosome abberation and oncogene activation in two histologically related human and rat B-cell tumors

Abstract

Activation of a cellular oncogene by chromosomal tanslocation which brings an oncogene under the influence of a highly active chromosome region appears to play a pivotal role in the genesis of certain hematopoetic and lymphoid tumors. This is most consistently seen in mouse plasmacytoma (MPC) where the MPC-associated specific chomosomal translocations bring the c-myc oncogene under the influence of the immunoglobulin heavy (IgH) or, more rarely, the kappa light chain gene. Closely homologous translocation activates the c-myc oncogene in human Burkitt Lymphoma (BL) and less frequently in other human B-cell lymphomas. The c-myc is transcriptionally activated by the integrated proviral DNA LTR region in avian bursal lymphoma. The critical effect of the translocation and proviral DNA integration is the constitutive expression of the c-myc oncogene. The purpose of our work over the past 2 years has been to investigate how stringent and general is the connection between DNA rearrangement, c-myc activation and the genesis of B-cell derived tumors. Our specific question was; is the perturbation of c-myc expression a consistent feature in the genesis of B-cell tumors of the same histological type. The nearest counterpart of the MPC is the human multiple myleoma (MM), plasma cell leukemia (PCL) and the rat spontaneous immunocytoma (RIC).