THE B-CELL TRANSCRIPTIONAL COACTIVATOR BOB1 OBF1 GENE FUSES TO THE LAZ3/BCL6 GENE BY T(3-11)(Q27-Q23.1) CHROMOSOMAL TRANSLOCATION IN A B-CELL LEUKEMIA LINE (KARPAS-231)/

The LAZ3/BCL6 gene on chromosome 3q27 is recurrently disrupted in B ce ll non-Hodgkin's lymphomas by translocations involving immunoglobulin genes or other chromosome regions. We have cloned the breakpoint regio n and chromosome derivatives of the t(3;11)(q27;q23.1) translocation, present in a B cell leukemia cell line (Karpas 231), which define a no vel 11q23.1 breakpoint site. As a consequence of the translocation, LA Z3 regulatory regions upstream of non-coding exon 2 are replaced by th ose of BOB1/OBF1, a recently described B cell-specific coactivator of octamer-binding transcription factors. A detailed structural study of the BOB1/OBF1 genomic DNA and of a nearly full-length cDNA revealed pa rticular features in the 3' untranslated region, such as an Alu motif and a polymorphic tetranucleotide microsatellite. Two mutations leadin g to two potential amino acid changes in the C-terminal region, were a lso detected in one allele of a lymphoma B cell line, Raji. Due to its cell-specific expression and role as a coactivating transcription fac tor, chromosomal translocation and/or point mutation of BOB1/OBF1 may contribute to B cell tumorigenesis.