Detection of recombinations between c-myc and immunoglobulin switch alpha in murine plasma cell tumors and preneoplastic lesions by polymerase chain reaction.
Virtually all murine plasmacytomas carry chromosomal translocations that activate c-myc. The predominant (approximately 90%) c-myc-activating chromosomal translocation in pristane (2,6,10,14-tetramethylpentadecane)-induced plasmacytomas in BALB/c mice is a reciprocal translocation t(12;15) in which an immunoglobulin heavy-chain switch sequence is joined to the 5' region of c-myc. The most common switch region involved is S alpha. We developed a direct PCR method to screen for recombinations between c-myc and S alpha. The critical step in establishing the method was the cloning and sequencing of the 5' flank of C alpha, a region with a reduced number of switch repeats that is much more favorable for designing specific PCR primers than the highly repetitive S alpha region. In applying this PCR method, we detected translocation-specific junction fragments in transplanted (10/16, 63%) and primary (5/15, 33%) plasmacytomas. Moreover, the sensitivity of a nested version of that technique allowed us to discern rare t(12;15)s in BALB/c mice in the preneoplastic stage of plasmacytoma-genesis (8/20 mice, 40%) as early as 30 days after administration of pristane. We conclude that t(12;15) is the probable primary, if not initiating, oncogenic step in plasmacytomagenesis.
Janz
S
S
Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814.
Müller
J
J
Shaughnessy
J
J
Potter
M
M
D000818:Animals; D001483:Base Sequence; D005803:Genes, Immunoglobulin; D005812:Genes, Switch; D016259:Genes, myc; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007132:Immunoglobulin Isotypes / Q000235:genetics; D007137:Immunoglobulin alpha-Chains / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010954:Plasmacytoma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000235:genetics*; D011995:Recombination, Genetic; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D007137:Immunoglobulin alpha-Chains; D009838:Oligodeoxyribonucleotides