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Updated: Jan 24, 2026

Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral Integration Sites
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Published on: March 22, 2016

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Genomic landscape analyses of reprogrammed cells using integrative and non-integrative methods reveal variable

Frank Griscelli1,2,3,4, Christophe Desterke5, Olivier Feraud1,2

  • 1Institut National de la Santé et de la Recherche Médicale (INSERM) U935, Paris, France.

Oncotarget
|May 21, 2019
PubMed

Insights

Human induced pluripotent stem cells (hiPSCs) hold promise for cell therapy. However, genetic screening is crucial as reprogramming methods can introduce cancer-associated genomic alterations, particularly with viral methods.

Area of Science:

  • Stem Cell Biology
  • Genomics
  • Cancer Research

Background:

  • Cell reprogramming technologies offer potential for cell therapy applications.
  • Ensuring genomic stability in induced pluripotent stem cells (iPSCs) is critical to prevent oncogenic transformation.
  • Non-integrative reprogramming methods are preferred to minimize risks associated with genetic manipulation.

Purpose of the Study:

  • To analyze copy number variations (CNVs) in human iPSCs (hiPSCs) generated by different reprogramming methods.
  • To assess genomic alterations in hiPSCs and their teratoma derivatives for cancer-associated gene deregulation.
  • To compare the safety profiles of integrative versus non-integrative hiPSC generation techniques.

Main Methods:

  • Microarray-based comparative genomic hybridization (aCGH) was employed to detect CNVs.
  • Human iPSCs were generated using two non-integrative (mRNA) and one integrative (viral) reprogramming methods.
  • Genomic analysis was performed on hiPSCs at the pluripotent stage and in corresponding teratomas.

Main Results:

  • All analyzed hiPSC lines exhibited copy number variations (CNVs) in genes linked to oncogenesis.
  • Cancer-associated genomic alterations were more prevalent in virally reprogrammed hiPSCs and their teratomas compared to mRNA-derived hiPSCs.
  • Bioinformatics analysis indicated the involvement of these deregulated genes in human leukemia and carcinoma.

Conclusions:

  • Reprogramming methods influence the genomic integrity of hiPSCs, with viral methods posing higher risks.
  • Cancer-associated genomic alterations are present in hiPSCs and their derivatives, necessitating careful evaluation.
  • Routine genetic screening for cancer-associated genomic alterations is recommended before clinical application of hiPSCs.
Keywords:
CGH arraygenetic instabilityiPSCs

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