Disease relevance of Pvt1

• 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 [1].
• Genetic mapping of a cellular DNA region involved in induction of thymic lymphomas (Mlvi-1) to mouse chromosome 15 [2].
• Since aberrations on chromosome 15 have been observed reproducibly in mouse thymomas, our data suggest that Mlvi -2 may define a novel sequence involved in the induction or progression of murine thymic lymphomas [3].
• Evidence presented elsewhere shows that provirus integration in Mlvi-4 enhances the expression of c-myc and Mlvi-1 by cis-acting mechanisms operating over long distances of genomic DNA [4].
• A chromosomal translocation (Tx) that interrupts the transcription of either c-Myc or Pvt 1 is the principal lesion in many B cell malignancies including Burkitt's Lymphoma (BL), AIDs-NHL, mouse plasmacytoma (Pct) and possibly multiple myeloma (MM) [5].

High impact information on Pvt1

• A probe derived from the conserved sequences 5' of the integrated proviruses detected a tumor-specific RNA transcript in tumors carrying a provirus in Mlvi-1 or in the neighboring Mlvi-4 and c-myc loci [6].
• The Mlvi-1/mis-1/pvt-1 locus, located approximately 270 kilobase pairs 3' of the c-myc protooncogene, was originally discovered as a common region of provirus integration in Moloney murine leukemia virus-induced rat T-cell lymphomas [6].
• Activation of the Mlvi-1/mis1/pvt-1 locus in Moloney murine leukemia virus-induced T-cell lymphomas [6].
• Systematic hybridization of Mlvi-1 clones to rat, mouse, and human genomic DNA revealed three patches of evolutionarily conserved sequences [6].
• The Mis-1 locus is a common proviral integration site in retrovirally induced rat T lymphomas, while the pvt-1 locus on murine chromosome 15 frequently translocates to the kappa locus in plasmacytomas bearing 6;15 translocations [7].

Biological context of Pvt1

• This defect may be responsible for the inability of normal BALB/cAnPt lymphoblasts to repair DNA sequences in the c-myc 5' flank and the Pvt1 gene, inducing gene-specific instability that predisposes these loci to genetic accidents, including chromosomal translocation, retroviral integration and other mutations [8].
• This finding indicates that, in BALB/cAnPt lymphoblasts, DNA repair 5' to c-myc and in Pvt1 is decoupled from the RNA transcription machinery [8].
• In this study, we identified the chromosomal map location of the Mlvi -2 homologous sequences in mice by using hamster-mouse somatic cell hybrids [3].
• Over the past several years, our laboratory has been instrumental in the elucidation of the structure of the mouse Pvt 1 locus as a means of understanding the relationship between these two divergent Txs which, nevertheless, produce indistinguishable disease phenotypes [5].
• The alpha-globin pseudogene, Hba-3ps, was mapped in close proximity to Mlvi-1 in 15D2 [9].

Anatomical context of Pvt1

• We have recently constructed transgenic mice harboring a translocated Pvt 1/Ck segment in order to determine whether 1). these mice produce the Pvt 1/Ck fusion product 2). these mice are immunocompromised and 3). these mice develop tumors of a B cell origin [5].
• The Mlvi-1 locus involved in the induction of rat T-cell lymphomas and the pvt-1/Mis-1 locus are identical [10].

Regulatory relationships of Pvt1

• Mlvi-1 defines a locus of proviral integration in rat thymomas induced by Moloney murine leukemia virus. pvt-1/Mis-1 represents an independently identified locus which becomes rearranged either by chromosomal translocation in murine plasmacytomas or by provirus insertion in retrovirus-induced murine and rat thymic lymphomas [10].
• A novel c-myc-activating reciprocal T(12;15) chromosomal translocation juxtaposes S alpha to Pvt-1 in a mouse plasmacytoma [11].

Other interactions of Pvt1

• The results show that Mlvi -2 is present on mouse chromosome 15 but is unrelated to the c-myc and c-sis proto-oncogenes, which map on the same chromosome [3].
• A co-distribution of PV-RFLPs with Pvt-1 and Mlvi-2, which had been localized on chromosome 15, was detected [12].
• Mlvi-1 defines a genetic locus representing a common domain for proviral DNA integration in Moloney murine leukemia virus-induced rat thymic lymphomas [2].
• In this study, we identified the chromosomal map location of Mlvi-1, Mlvi-2, and Mlvi-3 in the rat by using mouse-rat somatic cell hybrids that lose the rat chromosomes [13].
• c-myc gene in a murine plasmocytoma without visible chromosomal translocations moves to chromosome 12F1 with Pvt-1 and rearranges with IgH enhancer-S mu sequences [14].

Analytical, diagnostic and therapeutic context of Pvt1

• Although Mlvi-1 and c-myc map to the same chromosome, they are not related, as determined by hybridization and restriction endonuclease mapping [13].
• Further analysis by fluorescence in situ hybridization demonstrates that the amplicons of c-Myc and Pvt 1 exist as extrachromosomal elements as well as within intact chromosomes [15].

References