Translocation of c-myc into the immunoglobulin heavy-chain locus in human acute B-cell leukemia. A molecular analysis.
We report the molecular analysis of primary cells from four cases of human B-cell malignancies each with an 8;14 chromosomal translocation involving the c-myc proto-oncogene and the immunoglobulin (Ig) gene cluster. In two cases of B-cell acute lymphocytic leukemia (B-ALL) the c-myc is truncated, rearranged into the Ig C alpha 1 locus and over-expressed in two abnormal mRNAs of approximately 2.0 and 2.8 kb. Conversely, in two cases of B-cell lymphoma progressed into leukemia the c-myc locus was translocated intact in its coding and 5'-flanking region into an Ig region different from C alpha 1, and over-expressed in two normal mRNA species. Cloning and sequencing of the breakpoint region on chromosome 14q+ from one of the two B-ALL cases showed that the myc gene is truncated 1077 nucleotides upstream from the translation start site, and rearranged in the opposite transcriptional orientation into an Ig class-switch segment approximately 4.8 kb upstream from the C alpha 1 gene. The c-myc anti-sense strand contains two class-switch recombination consensus sequences in the immediate boundaries of the breakpoint on chromosome 8: this allows us to postulate that an erroneous, class-switch-like recombination between Ig and myc sequences gave rise to the chromosomal translocation. Furthermore, we report 13 point mutations clustered in a region spanning from the first intron to the second exon of the translocated c-myc gene, five of which cause amino acid changes leading to an abnormal myc protein. This is the first evidence of mutations in a translocated c-myc in primary tumor cells.
D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D002901:Chromosomes, Human, 13-15; D004262:DNA Restriction Enzymes; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007945:Leukemia, Lymphoid / Q000276:immunology*; D008297:Male; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D012016:Reference Values; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D004262:DNA Restriction Enzymes