A novel c-myc-activating reciprocal T(12;15) chromosomal translocation juxtaposes S alpha to Pvt-1 in a mouse plasmacytoma.
Oil-induced murine plasmacytomas typically carry c-myc-activating non-random reciprocal chromosomal translocations that take the form of either a T(12;15) that fuses the c-myc proto-oncogene to an immunoglobulin heavy chain switch region or a T(6;15) that juxtaposes the Pvt-1 locus, located 220 kb 3' of c-myc, to the immunoglobulin light china locus, C kappa. In this report we show that the plasmacytoma ABPC 60 harbors a novel c-myc-activating T(12;15) in which the chromosome 15 breakpoint occurs in the Pvt-1 region, resulting in the head-to-tail juxtaposition of the Pvt-1 major breakpoint cluster to the IgA switch region. Restriction mapping and nucleotide sequencing of this atypical translocation indicate that a paracentric inversion in chromosome 12 must have preceeded the translocation. This is the first example of a T(12;15) with a break 3' of the c-myc gene. The rearrangement places the 3' C alpha enhancer (3' alpha E) greater than 200 kb downstream of the c-myc promoters, however c-myc mRNA levels are similar to those observed in plasmacytomas with typical T(12;15)s that translocate 3' alpha E much closer (15-25 kb) and upstream of c-myc. The up regulation of c-myc that results from this rearrangement is thought to be brought about by the interaction of the c-myc promoters with the IgA enhancer element that has been strategically relocated into the Pvt-1 region.
Shaughnessy
J
J
Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892.
Wiener
F
F
Huppi
K
K
Mushinski
J F
JF
Potter
M
M
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D002884:Chromosomes, Human, Pair 15; D005260:Female; D015870:Gene Expression; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D016259:Genes, myc; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010954:Plasmacytoma / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D014178:Translocation, Genetic
D007070:Immunoglobulin A; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas