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Genomic instability in incuded stem cells and regulation of P14ARF expression

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Defense Thèse de doctorat : Univ. Genève, 2011 - Sc. 4335 - 2011/07/07
Abstract Part I. Genomic instability in induced stem cells - The ability to reprogram adult cells into stem cells has raised hopes for novel therapies. Expression of oncogenes leads to DNA replication stress and genomic instability, explaining the high frequency of p53 mutations in human cancers. We wondered whether stem cell reprogramming also leads to genomic instability. We examined stem cells induced by a variety of protocols. Comparative genomic hybridization analysis of stem cells revealed the presence of genomic deletions and amplifications, whose signature was suggestive of oncogene induced DNA replication stress. Part II. Regulation of p14ARF Expression - We examined the role of p14ARF in cancer. p14ARF is encoded by CDKN2A locus, which also encodes p16INK4A. By analysis of mRNA and protein levels, we found that E2F1 acts at the level of p14ARF mRNA. Identifying how p14ARF levels are regulated could be useful in therapeutic applications particularly in p53-defective cancers.
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URN: urn:nbn:ch:unige-170985
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DERELI, Ayguel. Genomic instability in incuded stem cells and regulation of P14ARF expression. Université de Genève. Thèse, 2011. https://archive-ouverte.unige.ch/unige:17098

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Deposited on : 2011-10-03

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