Alternative titles; symbols
HGNC Approved Gene Symbol: PVT1
Cytogenetic location: 8q24.21 Genomic coordinates (GRCh38): 8:127,794,524-128,101,256 (from NCBI)
In both mouse and man with t(6;15) and t(2;8) translocations, respectively, Graham and Adams (1986) identified a sequence, which they termed PVT1, that is involved in some human Burkitt lymphomas and murine plasma cytomas.
Graham and Adams (1986) found that the PVT1 sequence coamplified with MYC (190080) and was thought to lie about 100 to 500 kb 3-prime of MYC on chromosome 8.
Using chromosome engineering in mice, Tseng et al. (2014) showed that a single extra copy of either the Myc gene (190080) or the region encompassing Pvt1, Ccdc26 (613040), and Gsdmc (608384) fails to advance cancer measurably, whereas a single supernumerary segment encompassing all 4 genes successfully promotes cancer. Gain of PVT1 long noncoding RNA (lncRNA) expression was required for high MYC protein levels in 8q24-amplified human cancer cells. PVT1 RNA and MYC protein expression correlated in primary human tumors, and copy number of PVT1 was coincreased in more than 98% of MYC copy-increase cancers. Ablation of PVT1 from MYC-driven colon cancer cell line HCT116 diminished its tumorigenic potency. As MYC protein had been refractory to small-molecule inhibition, the dependence of high MYC protein levels on PVT1 lncRNA provided a therapeutic target.
Cho et al. (2018) found that CRISPR interference of the PVT1 promoter enhanced proliferation and competition in human breast cancer cells. Gene expression analysis showed that interference of the PVT1 promoter caused increased expression of MYC, which in turn promoted cell competition and proliferation in breast cancer cells in a PVT1 lncNA-independent manner. The PVT1 and MYC promoters, which are located 58 kb apart, competed for engagement with 4 intragenic enhancers in the PVT1 locus, thereby allowing the PVT1 promoter to suppress MYC transcription. This PVT1-MYC promoter competition was cell-type specific, and the dynamic interplay between PVT1 and MYC was coregulated through chromatin contacts. Studies in breast cancer cells demonstrated that regulation of PVT1 and MYC via promoter competition was bidirectional, as interference with the PVT1 promoter decreased MYC transcription, and interference with the MYC promoter increased PVT1 transcription. The authors measured chromatin accessibility, histone modification, and RNA transcripts in an allele-specific fashion in mouse cells and found that Pvt1 underwent developmentally regulated monoallelic expression, and that the Pvt1 promoter directly repressed Myc transcription only from the same chromosome via promoter competition.
Cho, S. W., Xu, J., Sun, R., Mumbach, M. R., Carter, A. C., Chen, Y. G., Yost, K. E., Kim, J., He, J., Nevins, S. A., Chin, S.-F., Caldas, C., Liu, S. J., Horlbeck, M. A., Lim, D. A., Weissman, J. S., Curtis, C., Chang, H. Y. Promoter of lncRNA gene PVT1 is a tumor-suppressor DNA boundary element. Cell 173: 1398-1412, 2018. [PubMed: 29731168] [Full Text: https://doi.org/10.1016/j.cell.2018.03.068]
Graham, M., Adams, J. M. Chromosome 8 breakpoint far 3-prime of the c-myc oncogene in a Burkitt's lymphoma 2;8 variant translocation is equivalent to the murine pvt-1 locus. EMBO J. 5: 2845-2851, 1986. [PubMed: 3024964] [Full Text: https://doi.org/10.1002/j.1460-2075.1986.tb04578.x]
Tseng, Y.-Y., Moriarity, B. S., Gong, W., Akiyama, R., Tiwari, A., Kawakami, H., Ronning, P., Reuland, B., Guenther, K., Beadnell, T. C., Essig, J., Otto, G. M., O'Sullivan, M. G., Largaespada, D. A., Schwertfeger, K. L., Marahrens, Y., Kawakami, Y., Bagchi, A. PVT1 dependence in cancer with MYC copy-number increase. Nature 512: 82-86, 2014. [PubMed: 25043044] [Full Text: https://doi.org/10.1038/nature13311]