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Updated: Jul 11, 2026

Retroviral Scanning: Mapping MLV Integration Sites to Define Cell-specific Regulatory Regions
Published on: May 28, 2017
Quantitative expression profiling guided by common retroviral insertion sites reveals novel and cell type specific
Martin Sauvageau1, Michelle Miller, Sébastien Lemieux
1Molecular Genetics of Stem Cells Laboratory, Institute for Research in Immunology and Cancer, University of Montreal, and Division of Hematology, Maisonneuve-Rosemont Hospital, Quebec, Canada.
Abstract:
Proviral insertional mutagenesis is a powerful tool for the discovery of cancer-associated genes. The ability of integrated proviruses to affect gene expression over long distances combined with the lack of methods to determine the expression levels of large numbers of genes in a systematic and truly quantitative manner have limited the identification of cancer genes by proviral insertional mutagenesis. Here, we have characterized a new model of proviral insertional mutagenesis-induced lymphoid tumors derived from Eed Polycomb group gene mutant mice and quantitatively determined the expression levels of all genes within 100 kb of 20 different retroviral common insertion sites (CISs) identified in these tumors. Using high-throughput quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR), we document an average of 13 CIS-associated genes deregulated per tumor, half of which are leukemia subtype-specific, while the others are coordinately deregulated in the majority of tumors analyzed. Interestingly, we find that genes located distantly from common proviral integration sites are as frequently deregulated as proximal genes, with multiple genes affected per integration. Our studies reveal an unsuspected conservation in the group of genes deregulated among phenotypically similar subtypes of lymphoid leukemias, and suggest that identification of common molecular determinants of this disease is within reach.
Insights
Proviral insertional mutagenesis can now identify more cancer genes. This study reveals deregulated genes near retroviral insertion sites, aiding lymphoid leukemia research.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Proviral insertional mutagenesis is valuable for discovering cancer genes.
- Limitations in gene expression analysis have hindered gene discovery.
- A new model using Eed Polycomb group gene mutant mice was developed.
Purpose of the Study:
- To characterize a new model of insertional mutagenesis-induced lymphoid tumors.
- To quantitatively determine gene expression levels near retroviral common insertion sites (CISs).
- To identify cancer-associated genes deregulated by proviral insertions.
Main Methods:
- Characterization of lymphoid tumors from Eed mutant mice.
- Identification of 20 retroviral common insertion sites (CISs).
- High-throughput quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR) to measure gene expression levels within 100 kb of CISs.
Main Results:
- An average of 13 CIS-associated genes were deregulated per tumor.
- Half of deregulated genes were leukemia subtype-specific; others were coordinately deregulated.
- Genes distant from CISs were as frequently deregulated as proximal genes, with multiple genes affected per integration.
Conclusions:
- The study identified a conserved group of deregulated genes in similar lymphoid leukemia subtypes.
- This approach advances the identification of common molecular determinants in lymphoid leukemias.
- The findings suggest a more comprehensive understanding of insertional mutagenesis in cancer gene discovery.
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