Cancer-related epigenome changes associated with reprogramming to induced pluripotent stem cells

Joyce E. Ohm, Prashant Mali, Leander Van Neste, David M. Berman, Liang Liang, Kurinji Pandiyan, Kimberly J. Briggs, Wei Zhang, Pedram Argani, Brian Simons, Wayne Yu, William Matsui, Wim Van Criekinge, Feyruz V. Rassool, Elias Zambidis, Kornel E. Schuebel, Leslie Cope, Jonathan Yen, Helai P. Mohammad, Linzhao ChengStephen B. Baylin

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Abstract

The ability to induce pluripotent stem cells from committed, somatic human cells provides tremendous potential for regenerative medicine. However, there is a defined neoplastic potential inherent to such reprogramming that must be understood and may provide a model for understanding key events in tumorigenesis. Using genome-wide assays, we identify cancer-related epigenetic abnormalities that arise early during reprogramming and persist in induced pluripotent stem cell (iPS) clones. These include hundreds of abnormal gene silencing events, patterns of aberrant responses to epigenetic-modifying drugs resembling those for cancer cells, and presence in iPS and partially reprogrammed cells of cancer-specific gene promoter DNA methylation alterations. Our findings suggest that by studying the process of induced reprogramming, we may gain significant insight into the origins of epigenetic gene silencing associated with human tumorigenesis, and add to means of assessing iPS for safety.

Original languageEnglish (US)
Pages (from-to)7662-7673
Number of pages12
JournalCancer Research
Volume70
Issue number19
DOIs
StatePublished - Oct 1 2010

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ohm, J. E., Mali, P., Van Neste, L., Berman, D. M., Liang, L., Pandiyan, K., Briggs, K. J., Zhang, W., Argani, P., Simons, B., Yu, W., Matsui, W., Van Criekinge, W., Rassool, F. V., Zambidis, E., Schuebel, K. E., Cope, L., Yen, J., Mohammad, H. P., ... Baylin, S. B. (2010). Cancer-related epigenome changes associated with reprogramming to induced pluripotent stem cells. Cancer Research, 70(19), 7662-7673. https://doi.org/10.1158/0008-5472.CAN-10-1361