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.

Blood
|October 2, 2007
PubMed

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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