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Le Macrosatellite RNU2: Caractérisation, Évolution Et Lien Avec La Prédisposition Génétique Au Cancer Du Sein

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Le Macrosatellite RNU2: Caractérisation, Évolution Et Lien Avec La Prédisposition Génétique Au Cancer Du Sein Le macrosatellite RNU2 : caractérisation, évolution et lien avec la prédisposition génétique au cancer du sein Chloé Tessereau To cite this version: Chloé Tessereau. Le macrosatellite RNU2 : caractérisation, évolution et lien avec la prédisposition génétique au cancer du sein. Génétique humaine. Université Claude Bernard - Lyon I, 2014. Français. NNT : 2014LYO10075. tel-01058217 HAL Id: tel-01058217 https://tel.archives-ouvertes.fr/tel-01058217 Submitted on 26 Aug 2014 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. N° d’ordre 75-2014 Année 2014 THESE DE L‘UNIVERSITE DE LYON Délivrée par L’UNIVERSITE CLAUDE BERNARD LYON 1 ECOLE DOCTORALE BIOLOGIE MOLECULAIRE INTEGRATIVE ET CELLULAIRE DIPLOME DE DOCTORAT (arrêté du 7 août 2006) soutenue publiquement le 16 Mai 2014 par Madame Chloé Tessereau TITRE : Le Macrosatellite RNU2 : Caractérisation, Evolution et Lien avec la Prédisposition Génétique au Cancer du Sein Directeur de thèse : Docteur Sylvie Mazoyer JURY : Docteur Sophie Gad (Examinateur) Docteur David Goldgar (Examinateur) Docteur Frédérique Magdinier (Rapporteur) Professeur Jean-Louis Mandel (Rapporteur) Docteur Sylvie Mazoyer (Directeur de Thèse) Professeur Damien Sanlaville (Examinateur) UNIVERSITE CLAUDE BERNARD - LYON 1 Président de l’Université M. François-Noël GILLY Vice-président du Conseil d’Administration M. le Professeur Hamda BEN HADID Vice-président du Conseil des Etudes et de la Vie Universitaire M. le Professeur Philippe LALLE Vice-président du Conseil Scientifique M. le Professeur Germain GILLET Directeur Général des Services M. Alain HELLEU COMPOSANTES SANTE Faculté de Médecine Lyon Est – Claude Bernard Directeur : M. le Professeur J. ETIENNE Faculté de Médecine et de Maïeutique Lyon Sud – Charles Mérieux Directeur : Mme la Professeure C. BURILLON Faculté d’Odontologie Directeur : M. le Professeur D. BOURGEOIS Institut des Sciences Pharmaceutiques et Biologiques Directeur : Mme la Professeure C. VINCIGUERRA Institut des Sciences et Techniques de la Réadaptation Directeur : M. le Professeur Y. MATILLON Département de formation et Centre de Recherche en Biologie Humaine Directeur : M. le Professeur P. FARGE COMPOSANTES ET DEPARTEMENTS DE SCIENCES ET TECHNOLOGIE Faculté des Sciences et Technologies Directeur : M. le Professeur F. DE MARCHI Département Biologie Directeur : M. le Professeur F. FLEURY Département Chimie Biochimie Directeur : Mme le Professeur H. PARROT Département GEP Directeur : M. N. SIAUVE Département Informatique Directeur : M. le Professeur S. AKKOUCHE Département Mathématiques Directeur : M. le Professeur A. GOLDMAN Département Mécanique Directeur : M. le Professeur H. BEN HADID Département Physique Directeur : Mme S. FLECK Département Sciences de la Terre Directeur : Mme la Professeure I. DANIEL UFR Sciences et Techniques des Activités Physiques et Sportives Directeur : M. C. COLLIGNON Observatoire des Sciences de l’Univers de Lyon Directeur : M. B. GUIDERDONI Polytech Lyon Directeur : M. P. FOURNIER Ecole Supérieure de Chimie Physique Electronique Directeur : M. G. PIGNAULT Institut Universitaire de Technologie de Lyon 1 Directeur : M. C. VITON Institut Universitaire de Formation des Maîtres Directeur : M. A. MOUGNIOTTE Institut de Science Financière et d'Assurances Administrateur provisoire : M. N. LEBOISNE – Page 2 sur 225 – Un roman, c’est un miroir qu’on promène le long d’un chemin. Stendhal, Le Rouge & Le Noir. A Mme Rozier, Mme Claire Vourc’h & Mr Olivier Bensaude qui m’ont initié au chemin de la Science, Au Dr Jaboulay qui a abrité 2190 nuits et jours d’échanges passionnants, A mon grand-père qui, s’endormant sur le canapé, m’a transmis sa patience, A Catherine, qui a livré un combat déchirant. – Page 3 sur 225 – Remerciements Ma première pensée s’adresse à ma directrice de thèse, Sylvie Mazoyer. Les mots ne suffiraient pas pour te remercier pour tout ce que tu m’as apporté. Pendant 5 ans, ton encadrement a été excellent, terme que nous détestons toutes les deux tout autant mais qui convient ici parfaitement. Tu as fait naître en mot l’envie de faire une thèse, en me proposant un sujet qui m’a passionnée. Je te remercie pour le savoir que tu m’as transmis, pour tes qualités humaines qui m’ont fait grandir, et pour le temps précieux que tu m’as accordée. J’espère que nos routes scientifiques se recroiseront souvent. En attendant, très sincèrement, merci. Je remercie Madame Frédérique Magdinier et Monsieur Jean-Louis Mandel pour avoir accepté d’évaluer ce manuscrit. Je remercie Madame Sophie Gad, Monsieur Damien Sanlaville et Monsieur David Goldgar pour m’avoir fait l’honneur de participer à mon jury de soutenance. Je remercie très sincèrement Monique Buisson, pour son aide au quotidien à la paillasse, pour son savoir qu’elle m’a transmis patiemment, pour les nombreuses relectures de ce manuscrit, mais surtout pour sa gentillesse et sa délicatesse. Travailler à tes côtés a été une chance dont je mesure l’importance. J’adresse mes remerciements à Gaël Yvert et Richard Redon, qui m’ont fait l’honneur de participer à mes trois comités de suivi de thèse et qui ont également su se montrer disponibles en d’autres occasions. Vos conseils ont été plus que bénéfiques. Pendant ma thèse, j’ai été entourée et j’ai eu la chance de rencontrer des personnes extraordinaires grâce auxquelles j’ai énormément appris, tant au niveau scientifique qu’humain. Quelques pages ne suffiraient pas à leur exprimer mon immense gratitude. Merci à Olga Sinilnikova et Mélanie Léoné pour leur gentillesse et leur aide. Merci à – Page 4 sur 225 – Laure Barjhoux, Carole Verny-Pierre et Valérie Sornin, qui font souvent un travail dans l’ombre et dont la contribution a été inestimable pour cette thèse. Merci à toutes les personnes du 1er étage du Cheney D (Cyril, Zaza, …) qui ont toujours été disponibles pour m’expliquer le fonctionnement de chaque instrument ou me prêter des feeders. Puisque les échanges scientifiques n’ont pas de frontière, j’ai eu la chance de réaliser ma thèse avec un financement CIFRE entre un laboratoire académique à Lyon, et la société Genomic Vision à Paris. Merci à Aaron Bensimon, Daniel Nerson et Erwan Martin pour avoir accepté de financer ma thèse et pour avoir nourri mon âme d’enfant en me permettant de peigner l’ADN. Merci à Sébastien Barradeau pour son soutien et nos échanges scientifiques à chacune de mes venues à Genomic Vision, à Jennifer Abscheidt, Marjorie Pierret et Stéphanie Bouchilloux pour leur gentillesse, leur dynamisme, et leur aide technique irremplaçable, à Kévin Cheeseman pour nos discussions passionnées sur la réalité de la vie de thésard, à Aurélie Thomas pour la formation qu’elle m’a prodiguée à mes débuts, à Emilie Renard pour toutes les commandes qu’elle a passées, à Fadilha Abut pour l’organisation de chacun de mes déplacements. Merci également à tous ceux qui se sont impliqués dans ce projet et avec qui les échanges scientifiques ont fait germer de nouvelles idées, dont Jun Komatsu et Lucia Cinque. Merci à toutes les personnes que j’ai citées précédemment et également Solène Guillon, Yannick Fourne, Djamila El Mhali, Samira Jbilou, Fanny Lemée, Sara Berthoumieux, Agnès Cibiel, Alexandra Nghe, pour leur bonne humeur qui accompagnait mes journées à la pépinière de Cochin puis à Bagneux. Un clin d’oeil tout particulier à mes compagnons de crop qui se reconnaitront… Ces quatre années ont été parsemées de quelques départs. Je tiens donc à remercier Anne Vannier, qui m’a formée à la technique du peignage moléculaire et qui a été à l’origine du premier marquage de la version 1.0 du code-barres RNU2. Merci à Emmanuel Conseiller qui a cru à mon projet et me l’a montré au moins un jeudi par mois. Enfin, merci à Quynh Dao Joyez, Mimounia et Rachel Morra. – Page 5 sur 225 – Un merci tout particulier à Laurent Duret, qui m’a accueillie au sein de son équipe pendant quelques mois et a su faire preuve de patience pour m’initier au monde merveilleux de la bio-informatique. Merci également à Yann Lesecque, Sylvain Mousset et Mathieu Groussin pour leur assistance technique et scientifique face à R, Perl, et cie … Merci également à Thomas Bigot pour ses conseils pointus sur ce manuscrit. Bien évidemment, merci à tous les membres du LBBE, toujours souriants et bienveillants lors de mon séjour prolongé ou de mes excursions passagères. Je remercie également Damien Sanlaville et Caroline Schluth-Bolard, qui m’ont accueillie dans leurs locaux à Bron et m’ont formée à la technique de FISH. Merci également à toutes les techniciennes de l’équipe pour leur gentillesse et leur aide. Merci à Marc Billaud qui m’a accueillie dans son laboratoire, l’UMR5201, pour la réalisation de mon Master 2. Merci à Alain Puisieux qui m’a accueillie au sein du Centre de Recherche en Cancérologie de Lyon pour mes trois dernières années de thèse. Merci à Daniel Birnbaum et Anne Le Tessier pour notre rencontre à Marseille qui a ouvert de nouvelles perspectives à ce projet : l’exploration de la fragilité du locus. Merci à Michelle Debatisse pour ses conseils lors de notre rencontre à Paris. Merci également à Arnaud Coquelle pour l’intérêt immédiat qu’il a manifesté pour cette hypothèse, pour le temps passé lors de notre rencontre à Montpellier, et pour son implication depuis. J’espère sincèrement que cela conduira à de belles choses. Merci à Olga Sinilnikova, Dominique Stoppat-Lyonnet et Nadine Andrieu pour m’avoir permis d’utiliser la cohorte GENESIS.
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