title: Burkitt lymphoma cell line carrying a variant translocation creates new DNA at the breakpoint and violates the hierarchy of immunoglobulin gene rearrangement.
abstract: The Burkitt lymphoma cell line KK124, which contains a reciprocal t(8;22) translocation, was shown to have rearranged in a region 3' to the c-myc proto-oncogene on chromosome 8 and 5' to the lambda constant region on chromosome 22. The breakpoint was cloned and sequenced, revealing that c-myc and a portion of its 3' region abutted a complete lambda variable gene that had undergone V-J recombination. Since this cell line expresses kappa light chain, this lambda rearrangement violates the previously proposed hierarchy of immunoglobulin gene rearrangement. A novel duplication of normal chromosome 8 sequences was also found at the breakpoint. The first exon of c-myc and its flanking sequence from the translocated allele was sequenced and compared with a normal counterpart. Extensive mutation was found within the first exon in contrast to its 3' and 5' flanking regions. S1 nuclease analysis revealed that it was the translocated c-myc being expressed and that there was a promoter shift from P2 to P1. The detailed structural analysis of this cell line provides clues concerning mechanisms of chromosomal translocation and c-myc deregulation in Burkitt lymphomas.
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D002906:Chromosomes, Human, 6-12 and X; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes; D004273:DNA, Neoplasm / Q000235:genetics*; D005796:Genes; D014644:Genetic Variation; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D014178:Translocation, Genetic
chemical_list: D004273:DNA, Neoplasm; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D004262:DNA Restriction Enzymes