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Murine leukemia virus-induced T-cell lymphomagenesis: integration of proviruses in a distinct chromosomal region
Abstract:
A number of mink cell focus-forming (MCF) proviruses was molecularly cloned from mouse lymphoma DNA. From each clone, flanking probes were prepared to detect common integration regions in other MuLV-induced lymphomas. One clone frequently revealed variations in the molecular structure of the corresponding region (Pim-1) in other lymphomas. The results show the following. Changes in the Pim region are seen in 24 out of 93 lymphomas tested. Over 50% of the early T-cell lymphomas show integration in the Pim-1 region. The alterations are seen in different mouse strains and with various MuLVs. The observed variations are caused by the integration of predominantly MCF genomes. All integrations occur in a region spanning less than 20 kb and are associated with the transcriptional activation of a distinct region within the Pim-1 domain. The activated region does not show any homology with 13 known and three putative oncogenes.
Insights
Mouse retroviral integrations, particularly mink cell focus-forming (MCF) proviruses, frequently alter the Pim-1 region in lymphomas. This activation occurs within a small genomic domain and is linked to early T-cell lymphoma development.
Area of Science:
- Molecular Biology
- Virology
- Oncology
Background:
- Mouse retroviruses, including mink cell focus-forming (MCF) proviruses, are implicated in lymphomagenesis.
- Understanding common integration sites is crucial for identifying viral oncogenes.
Purpose of the Study:
- To molecularly clone MCF proviruses from mouse lymphoma DNA.
- To identify common viral integration regions in MuLV-induced lymphomas.
- To investigate alterations in the Pim-1 region associated with lymphoma development.
Main Methods:
- Molecular cloning of MCF proviruses.
- Preparation of flanking probes for Southern blot analysis.
- Analysis of viral integration sites and gene expression in lymphoma DNA.
Main Results:
- Variations in the Pim-1 region were detected in 24 out of 93 lymphomas.
- Over 50% of early T-cell lymphomas showed integration in the Pim-1 region.
- Integrations, predominantly MCF genomes, occurred within a <20 kb region, activating a distinct domain within Pim-1 without homology to known oncogenes.
Conclusions:
- MCF virus integration is a common event in mouse lymphomas, specifically targeting the Pim-1 region.
- Pim-1 region alterations are associated with transcriptional activation and early T-cell lymphoma development.
- The activated region within Pim-1 does not represent known oncogenes, suggesting a novel mechanism of oncogenesis.
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