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 Cheng & 1 others Stephen B. Baylin

Research output: Contribution to journalArticle

50 Citations (Scopus)

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

Fingerprint

Induced Pluripotent Stem Cells
Epigenomics
Gene Silencing
Carcinogenesis
Neoplasms
Pluripotent Stem Cells
Regenerative Medicine
Neoplasm Genes
DNA Methylation
Clone Cells
Genome
Safety
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ohm, J. E., Mali, P., Van Neste, L., Berman, D. M., Liang, L., Pandiyan, K., ... 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

Cancer-related epigenome changes associated with reprogramming to induced pluripotent stem cells. / Ohm, Joyce E.; Mali, Prashant; Van Neste, Leander; Berman, David M.; Liang, Liang; Pandiyan, Kurinji; Briggs, Kimberly J.; Zhang, Wei; Argani, Pedram; Simons, Brian; Yu, Wayne; Matsui, William; Van Criekinge, Wim; Rassool, Feyruz V.; Zambidis, Elias; Schuebel, Kornel E.; Cope, Leslie; Yen, Jonathan; Mohammad, Helai P.; Cheng, Linzhao; Baylin, Stephen B.

In: Cancer Research, Vol. 70, No. 19, 01.10.2010, p. 7662-7673.

Research output: Contribution to journalArticle

Ohm, JE, Mali, P, Van Neste, L, Berman, DM, Liang, L, Pandiyan, K, Briggs, KJ, Zhang, W, Argani, P, Simons, B, Yu, W, Matsui, W, Van Criekinge, W, Rassool, FV, Zambidis, E, Schuebel, KE, Cope, L, Yen, J, Mohammad, HP, Cheng, L & Baylin, SB 2010, 'Cancer-related epigenome changes associated with reprogramming to induced pluripotent stem cells', Cancer Research, vol. 70, no. 19, pp. 7662-7673. https://doi.org/10.1158/0008-5472.CAN-10-1361
Ohm, Joyce E. ; Mali, Prashant ; Van Neste, Leander ; Berman, David M. ; Liang, Liang ; Pandiyan, Kurinji ; Briggs, Kimberly J. ; Zhang, Wei ; Argani, Pedram ; Simons, Brian ; Yu, Wayne ; Matsui, William ; Van Criekinge, Wim ; Rassool, Feyruz V. ; Zambidis, Elias ; Schuebel, Kornel E. ; Cope, Leslie ; Yen, Jonathan ; Mohammad, Helai P. ; Cheng, Linzhao ; Baylin, Stephen B. / Cancer-related epigenome changes associated with reprogramming to induced pluripotent stem cells. In: Cancer Research. 2010 ; Vol. 70, No. 19. pp. 7662-7673.
@article{8c84383800834604b52ec11bbc519dbf,
title = "Cancer-related epigenome changes associated with reprogramming to induced pluripotent stem cells",
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.",
author = "Ohm, {Joyce E.} and Prashant Mali and {Van Neste}, Leander and Berman, {David M.} and Liang Liang and Kurinji Pandiyan and Briggs, {Kimberly J.} and Wei Zhang and Pedram Argani and Brian Simons and Wayne Yu and William Matsui and {Van Criekinge}, Wim and Rassool, {Feyruz V.} and Elias Zambidis and Schuebel, {Kornel E.} and Leslie Cope and Jonathan Yen and Mohammad, {Helai P.} and Linzhao Cheng and Baylin, {Stephen B.}",
year = "2010",
month = "10",
day = "1",
doi = "10.1158/0008-5472.CAN-10-1361",
language = "English (US)",
volume = "70",
pages = "7662--7673",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "19",

}

TY - JOUR

T1 - Cancer-related epigenome changes associated with reprogramming to induced pluripotent stem cells

AU - Ohm, Joyce E.

AU - Mali, Prashant

AU - Van Neste, Leander

AU - Berman, David M.

AU - Liang, Liang

AU - Pandiyan, Kurinji

AU - Briggs, Kimberly J.

AU - Zhang, Wei

AU - Argani, Pedram

AU - Simons, Brian

AU - Yu, Wayne

AU - Matsui, William

AU - Van Criekinge, Wim

AU - Rassool, Feyruz V.

AU - Zambidis, Elias

AU - Schuebel, Kornel E.

AU - Cope, Leslie

AU - Yen, Jonathan

AU - Mohammad, Helai P.

AU - Cheng, Linzhao

AU - Baylin, Stephen B.

PY - 2010/10/1

Y1 - 2010/10/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77957365009&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957365009&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-10-1361

DO - 10.1158/0008-5472.CAN-10-1361

M3 - Article

VL - 70

SP - 7662

EP - 7673

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 19

ER -