Genomic landscape analyses of reprogrammed cells using integrative and non-integrative methods reveal variable cancer-associated alterations
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Frank Griscelli1,2,3,4, Christophe Desterke5, Olivier Feraud1,2, Dominique Divers1,2, Noufissa Oudrhiri1,2,6, Lucie Tosca1,5, Ali G. Turhan1,2,4,5 and Annelise Bennaceur-Griscelli1,2,4,5
1 Institut National de la Santé et de la Recherche Médicale (INSERM) U935, Paris, France
2 Human Embryonic Stem Cell Core Facility, ESTeam Paris Sud-INGESTEM, Villejuif, France
3 Université Paris Descartes, Sorbonne Paris Cité, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France
4 Institut Gustave-Roussy, Département de Biologie et de Pathologie Médicales, Villejuif, France
5 Université Paris-Sud, Faculté de Médecine Kremlin Bicêtre, Le Kremlin-Bicêtre, France
6 Service d’Hématologie Biologique, Hôpital Universitaire Paris Sud, (AP-HP) Kremlin Bicêtre, Le Kremlin-Bicêtre, France
Keywords: iPSCs; genetic instability; CGH array
Received: September 25, 2018 Accepted: March 23, 2019 Published: April 12, 2019
Recent development of cell reprogramming technologies brought a major hope for future cell therapy applications by the use of these cells or their derivatives. For this purpose, one of the major requirements is the absence of genomic alterations generating a risk of cell transformation. Here we analyzed by microarray-based comparative genomic hybridization human iPSC generated by two non-integrative and one integrative method at pluripotent stage as well as in corresponding teratomas. We show that all iPSC lines exhibit copy number variations (CNV) of several genes deregulated in oncogenesis. These cancer-associated genomic alterations were more pronounced in virally programmed hiPSCs and their derivative teratoma as compared to those found in iPSC generated by mRNA-mediated reprogramming. Bioinformatics analysis showed the involvement of these genes in human leukemia and carcinoma. We conclude that genetic screening should become a standard procedure to ensure that hiPSCs are free from cancer-associated genomic alterations before clinical use.
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