Huppi K, Siwarski D, Skurla R, Klinman D, Mushinski J F
Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1990 Sep;87(18):6964-8. doi: 10.1073/pnas.87.18.6964.
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.
小鼠Pvt-1（浆细胞瘤变异易位）区域定位于15号染色体的一个断点区域，该区域在浆细胞瘤中经常被“变异”的相互染色体易位rcpt(6;15)打断。该区域位于小鼠c-myc基因（Myc）下游数百千碱基（kb）处，在rcpt(6;15)和rcpt(12;15)浆细胞瘤中该基因均失调。rcpt(12;15)易位显然通过打断基因本身直接激活c-myc，但在携带rcpt(6;15)易位的肿瘤中导致c-myc失调的机制仍不清楚。Pvt-1中断间接激活c-myc仍然是一种有吸引力的可能性，但迄今为止还无法建立这样的联系。此外，尚未发现来自Pvt-1基因座的基因在正常组织或具有rcpt(6;15)易位的肿瘤中被转录。我们报告了从小鼠脾脏mRNA中分离出一个特异性针对Pvt-1区域的cDNA克隆Pvt-1-1。该cDNA探针在正常小鼠组织中检测到低水平的大（约14 kb）RNA转录本。在具有rcpt(6;15)易位的浆细胞瘤中，Pvt-1转录本的丰度升高且大小截短。这两种变化显然都是由染色体易位诱导的。14 kb的Pvt-1 RNA在表达免疫球蛋白轻链基因的B细胞肿瘤系中表达升高；因此，我们推测当免疫球蛋白κ轻链和Pvt-1基因在B细胞个体发育的特定时间同时表达时，它们DNA可及性的增加促进了这些易位。
