Pvt-1 transcripts are found in normal tissues and are altered by reciprocal(6;15) translocations in mouse plasmacytomas.
The mouse Pvt-1 (for plasmacytoma variant translocation) region maps to a chromosome 15 breakpoint region that is frequently interrupted by "variant" reciprocal chromosome translocations, rcpt(6;15), in plasmacytomas. This region lies several hundred kilobases (kb) 3' of the mouse c-myc gene (Myc) which is deregulated in both rcpt(6;15) and rcpt(12;15) plasmacytomas. rcpt(12;15) translocations apparently activate c-myc directly by interrupting the gene itself, but the mechanism causing c-myc deregulation in tumors bearing rcpt(6;15) translocations remains unknown. The indirect activation of c-myc by Pvt-1 interruption has remained an appealing possibility, but heretofore it has not been possible to establish such a connection. Furthermore, no genes from the Pvt-1 locus have been shown to be transcribed in normal tissues or in tumors with rcpt(6;15) translocations. We report the isolation of a cDNA clone, Pvt-1-1, from mouse spleen mRNA that is specific to the Pvt-1 region. This cDNA probe detects low levels of large (ca. 14 kb) RNA transcripts in normal mouse tissues. In plasmacytomas with rcpt(6;15) translocations, the Pvt-1 transcripts are elevated in abundance and truncated in size. Both changes are apparently induced by the chromosomal translocation. Expression of 14-kb Pvt-1 RNA is elevated in B-cell tumor lines that express immunoglobulin light chain genes; thus, we postulate that these translocations are facilitated by the increased DNA accessibility of immunoglobulin kappa light chain and Pvt-1 genes when they are simultaneously expressed at certain times during B-cell ontogeny.
Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
K
K
Huppi
D
D
Siwarski
R
R
Skurla
D
D
Klinman
J F
JF
Mushinski
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D015342:DNA Probes; D015723:Gene Library; D051379:Mice; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010954:Plasmacytoma / Q000235:genetics*; D012016:Reference Values; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014178:Translocation, Genetic
D015342:DNA Probes