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Dsi-1, a region with frequent proviral insertions in Moloney murine leukemia virus-induced rat thymomas
Abstract:
Dsi-1 is a region of chromosomal DNA that underwent proviral insertion in 3 of 24 Moloney murine leukemia virus-induced rat thymomas. In one of these tumors, a provirus is also integrated adjacent to the proto-oncogene c-myc. The proviruses in Dsi-1 have been characterized and appear to be complete. The proviruses were located within a 2-kilobase region that contained four prominent DNase I-hypersensitive sites. These hypersensitive sites were observed in Moloney murine leukemia virus-induced thymomas but not in NRK cells. The region of Dsi-1 immediately 3' to the insertions cross-hybridized with human and chicken DNA, indicating that it contains highly conserved sequences. No evidence could be found for the expression of this highly conserved region. Dsi-1 was mapped to mouse chromosome 4. This location demonstrates that Dsi-1 is different from 16 of the known proto-oncogenes (c-abl, c-erbA c-erbB, c-ets-1, c-ets-2, c-fes, c-fos, c-myb, c-myc, c-raf, A-raf, c-Ha-ras, c-Ki-ras, N-ras, c-sis, and c-src) and 12 cellular regions of tumor-associated integrations in retrovirus-induced tumors (c-erbB, Fis-1, int-1, int-2, Mis-1/pvt-1, Mlvi-1, Mlvi-2, c-mos, c-myb, c-myc, Pim-1, and c-Ha-ras). Hybridization experiments indicated that Dsi-1 is probably different from five additional proto-oncogenes (c-fgr, c-fms, c-mos, neu, and c-yes) and from two additional frequent integration regions (lck and Mlvi-3).
Insights
A novel DNA region, Dsi-1, was identified in rat thymomas induced by Moloney murine leukemia virus. This conserved region, located on mouse chromosome 4, is distinct from known oncogenes and integration sites.
Area of Science:
- * Molecular Biology
- * Oncology
- * Virology
Background:
- * Moloney murine leukemia virus (MMLV) can induce thymomas in rats through proviral DNA insertion.
- * Identifying specific DNA integration sites is crucial for understanding oncogenesis.
Purpose of the Study:
- * To characterize a novel DNA region, Dsi-1, identified by MMLV proviral insertion in rat thymomas.
- * To determine the genomic location and conservation of Dsi-1.
- * To differentiate Dsi-1 from known oncogenes and common retroviral integration sites.
Main Methods:
- * Analysis of proviral insertion sites in MMLV-induced rat thymomas.
- * DNA hybridization techniques to assess sequence conservation and compare with known genes.
- * Chromosomal mapping of the Dsi-1 region.
Main Results:
- * Dsi-1 was identified as a site of proviral insertion in 3 out of 24 rat thymomas.
- * Proviruses were located within a 2-kilobase region containing DNase I-hypersensitive sites specific to thymomas.
- * Dsi-1 contains highly conserved sequences but showed no evidence of expression; it was mapped to mouse chromosome 4, distinct from numerous known oncogenes and integration sites.
Conclusions:
- * Dsi-1 represents a novel, conserved DNA region implicated in MMLV-induced rat thymomas.
- * Its unique chromosomal location and lack of expression suggest a role independent of known oncogenes.
- * Further investigation into Dsi-1's function in tumorigenesis is warranted.