Global loss of imprinting leads to widespread tumorigenesis in adult mice

Cancer Cell. 2005 Oct;8(4):275-85. doi: 10.1016/j.ccr.2005.09.007.


Loss of imprinting (LOI), commonly observed in human tumors, refers to loss of monoallelic gene regulation normally conferred by parent-of-origin-specific DNA methylation. To test the function of LOI in tumorigenesis, we developed a model by using transient demethylation to generate imprint-free mouse embryonic stem cells (IF-ES cells). Embryonic fibroblasts derived from IF-ES cells (IF-MEFs) display TGFbeta resistance and reduced p19 and p53 expression and form tumors in SCID mice. IF-MEFs exhibit spontaneous immortalization and cooperate with H-Ras in cellular transformation. Chimeric animals derived from IF-ES cells develop multiple tumors arising from the injected IF-ES cells within 12 months. These data demonstrate that LOI alone can predispose cells to tumorigenesis and identify a pathway through which immortality conferred by LOI lowers the threshold for transformation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Transformed
  • DNA Methylation
  • DNA Primers
  • Genomic Imprinting*
  • Germ-Line Mutation
  • Mice
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / pathology*
  • Polymerase Chain Reaction


  • DNA Primers