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Étude du transcriptome des rétrovirus endogènes humains et implications fonctionnelles : applications à la recherche de marqueurs diagnostiques de cancers

Abstract : The human genome contains around 200,000 endogenous retroviral sequences (HERV) integrated during the evolution and which are nowadays organized into complex multicopy families, globally repressed by epigenetic control. The study of the HERV transcriptome at the locus level is complicated by phylogenetic similarities within one family and by the profusion of integration sites, two inherent characteristics of transposable elements. In this work, we used a method aiming to optimally characterize individual loci associated with 25 mer probes. A custom microarray dedicated to more than 5,500 HERV sequences and allowing a functional interpretation of the LTRs expression was used on a panel of normal and tumor tissues. We therefore identified 1,718 active HERV sequences, including 326 promoter LTRs and 209 polyA LTRs. The study of the genomic environment has highlighted an approximately 8 kb zone upstream of promoter LTRs characterized by a drastic reduction in sense cellular genes. We also showed that the HERV transcriptome follows tropism rules, is sensitive to the state of cell differentiation and, unexpectedly, seems not to correlate with the age of the families. In a first attempt to use the HERV repertoire in clinical, we sought to identify new markers of prostate cancer from urine samples. This goal was pursued by conducting a pilot study on 45 patients
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Philippe Perot. Étude du transcriptome des rétrovirus endogènes humains et implications fonctionnelles : applications à la recherche de marqueurs diagnostiques de cancers. Génomique, Transcriptomique et Protéomique [q-bio.GN]. Université Claude Bernard - Lyon I, 2012. Français. ⟨NNT : 2012LYO10228⟩. ⟨tel-01726971⟩

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