Genomic organization and expression of the rearranged REL proto‐oncogene in the human B‐cell lymphoma cell line RC‐K8

Abstract

The human large B-cell lymphoma cell line RC-K8 has a rearranged REL locus that is transcribed into a chimeric mRNA, termed REL-NRG (Non-Rel Gene). By analyzing the recently completed human genome sequence, we have found that the normal REL and NRG loci are separated by approximately 28 megabase pairs on chromosome 2, suggesting that a deletion created the REL-NRG locus in RC-K8 cells. Using computer-based and molecular approaches, we have determined the structure of the altered REL locus in RC-K8 cells. The REL-NRG transcript is encoded by 7 REL exons and 6 NRG-derived exons. Direct DNA sequencing has identified the site of the REL-NRG fusion in RC-K8 cells. We also show that both wild-type c-Rel and c-Rel-Nrg proteins are expressed and in a complex in RC-K8 cells. Furthermore, like c-Rel, c-Rel-Nrg is a cytoplasmic protein when overexpressed in fibroblasts in culture and can bind to a kappaB DNA site in vitro.