title: Mutations in the coding region of c-myc occur independently of mutations in the regulatory regions and are predominantly associated with myc/Ig translocation.
abstract: Constitutive expression of c-myc resulting from a chromosomal translocation, which juxtaposes c-myc to an immunoglobulin gene, is a pivotal lesion in Burkitt's lymphomas. This deregulated expression of c-myc is associated with mutations in the regulatory regions, i.e. the first exon and the first intron of c-myc in tumors where the chromosomal breakpoint is not itself within the regulatory region. Until recently it was widely believed that the c-myc protein in these tumors is wild type. We have demonstrated that in a fraction of Burkitt's lymphomas from Africa and from the continental USA, and in mouse plasmacytomas, the c-myc gene carries mutations in the coding region. We now show that, occasionally, such mutations are also present in multiple myelomas--tumors which do not carry translocations or amplifications of c-myc. We also show that the frequency of the c-myc coding region mutations in BL is independent of the frequency of mutations in the regulatory region. These results suggest that the mechanisms that induce missense mutations involving the coding region of c-myc may be different from those that lead to mutations in the regulatory regions.
authors.affiliation: Lymphoma Biology Section, NCI, NIH, Bethesda, MD 20892.
authors.forename: K
authors.initials: K
authors.lastname: Bhatia
authors.forename: G
authors.initials: G
authors.lastname: Spangler
authors.forename: N
authors.initials: N
authors.lastname: Hamdy
authors.forename: A
authors.initials: A
authors.lastname: Neri
authors.forename: G
authors.initials: G
authors.lastname: Brubaker
authors.forename: A
authors.initials: A
authors.lastname: Levin
authors.forename: I
authors.initials: I
authors.lastname: Magrath
mesh_terms: D002051:Burkitt Lymphoma / Q000235:genetics* / Q000821:virology; D002898:Chromosomes, Human, Pair 8 / Q000648:ultrastructure*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005803:Genes, Immunoglobulin; D016259:Genes, myc; D006566:Herpesviridae Infections / Q000235:genetics / Q000821:virology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007952:Leukemia, Plasma Cell / Q000235:genetics*; D009101:Multiple Myeloma / Q000235:genetics*; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D014178:Translocation, Genetic; D014412:Tumor Virus Infections / Q000235:genetics / Q000821:virology
chemical_list: D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains