B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-κB p50

A B cell lymphoma-associated chromosomal translocation, t(10;14)(q24;q32), juxtaposes the immunoglobulin Cα₁ locus to a novel gene, lyt-10. The normal lyt-10 cDNA codes for a 98 kd protein which displays amino-terminal homology with the rel (DNA-binding) domain of the NF-κB-rel family of transcription factors and carboxy-termlnal homology with the NF-κB p50 precursor protein, including the putative proteolytic cleavage domain (poly-G) and the ankyrin-like repeat domains. The lyt-10 protein can bind to κB sequences in vitro, although with different specificity from NF-κB p50, and in vitro DNA-binding is activated by removal of the ankyrin domain. Chromosomal translocation generates an lyt-10-Cα₁ fusion gene coding for a protein that retains the rel effector domain, lacks the ankyrin regulatory domain, and binds κB sequences in vitro, suggesting its constitutive activation in vivo. Analogous rearrangements of the lyt-10 gene have been found in an additional three cases of lymphoid neoplasia. The lyt-10 gene defines a new subfamily (rel/poly-G/ankyrin) of NF-κB-rel transcription factors with potential for oncogenic activation in human cancer.