The c-MYC allele that is translocated into the IgH locus undergoes constitutive hypermutation in a Burkitt's lymphoma line.
Burkitt's lymphomas harbour chromosomal translocations bringing c-MYC into the vicinity of one of the immunoglobulin gene loci. Point mutations have been described within c-MYC in several Burkitt's lymphomas and it has been proposed that translocation into the Ig loci might have transformed c-MYC into a substrate for the antibody hypermutation mechanism. Here we test this hypothesis by exploiting a Burkitt's lymphoma line (Ramos) that we have previously shown to hypermutate its immunoglobulin genes constitutively. We find that, during in vitro culture, Ramos mutates the c-MYC allele that is translocated into the IgH locus whilst leaving the untranslocated c-MYC and other control genes essentially unaffected. The mutations are introduced downstream of the c-MYC transcription start with the pattern of substitutions being characteristic of the antibody hypermutation mechanism; the mutation frequency is 2-3-fold lower than for the endogenous functional IgH allele. Thus chromosomal translocations involving the Ig loci may not only contribute to transformation by deregulating oncogene expression but could also act by potentiating subsequent oncogene hypermutation.
Bemark
M
M
MRC Laboratory of Molecular Biology, Cambridge, UK.
Neuberger
M S
MS
D000483:Alleles; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D016271:Proto-Oncogene Proteins c-myc