Aberrant epigenetic silencing of tumor suppressor genes is reversed by direct reprogramming

Shulamit Ron-Bigger, Ori Bar-Nur, Sara Isaac, Michael Bocker, Frank Lyko, Amir Eden*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Direct reprogramming procedures reset the epigenetic memory of cells and convert differentiated somatic cells into pluripotent stem cells. In addition to epigenetic memory of cell identity, which is established during development, somatic cells can accumulate abnormal epigenetic changes that can contribute to pathological conditions. Aberrant promoter hypermethylation and epigenetic silencing of tumor suppressor genes (TSGs) are now recognized as an important mechanism in tumor initiation and progression. Here, we have studied the fate of the silenced TSGs p16(CDKN2A) during direct reprogramming. We find that following reprogramming, p16 expression is restored and is stably maintained even when cells are induced to differentiate. Large-scale methylation profiling of donor cells identified aberrant methylation at hundreds of additional sites. Methylation at many, but not all these sites was reversed following reprogramming. Our results suggest that reprogramming approaches may be applied to repair the epigenetic lesions associated with cancer.

Original languageAmerican English
Pages (from-to)1349-1354
Number of pages6
JournalStem Cells
Issue number8
StatePublished - Aug 2010


  • Cancer epigenetics
  • DNA methylation
  • iPS reprogramming


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