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 chromosone 3q27 is recurrently disrupted in B cell non-Hodgkin's lymphomas by translocations involving immunoglobulin genes or other chromosone regions. We have cloned the breakpoint region and chromosone derivatives of the t(3;11)(q27;q23.1) translocation, present in a B cell leukemia cell line (Karpas 231), which define a novel 11q23.1 breakpoint site. As a consequence of the translocation, LAZ3 regulatory regions upstream of non-coding exon 2 are replaced by those 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 particular features in the 3' untranslated region, such as an Alu motif and a polymorphic tetranucleotide microsatellite. Two mutations leading to two potential amino acid changes in the C-terminal region, were also detected in one allele of a lymphoma B cell line, Raji. Due to its cell-specific expression and role as a coactivating transcription factor, chromosomal translocation and/or point mutation of BOB1/OBF1 may contribute to B cell tumorigenesis.
Galiègue Zouitina
S
S
Unité 124 INSERM, Institut de Recherches sur le Cancer de Lille, France.
Quief
S
S
Hildebrand
M P
MP
Denis
C
C
Lecocq
G
G
Collyn-d'Hooghe
M
M
Bastard
C
C
Yuille
M
M
Dyer
M J
MJ
Kerckaert
J P
JP
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002893:Chromosomes, Human, Pair 3; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005091:Exons; D015870:Gene Expression; D005803:Genes, Immunoglobulin; D006801:Humans; D007438:Introns; D015448:Leukemia, B-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
C084103:BCL6 protein, human; D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C091546:POU2AF1 protein, human; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D015534:Trans-Activators; D014157:Transcription Factors