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dc.contributor.advisorDrouin, Régenfr
dc.contributor.advisorYan, Jufr
dc.contributor.authorSamassékou, Oumarfr
dc.date.accessioned2014-09-09T18:39:32Z
dc.date.available2014-09-09T18:39:32Z
dc.date.created2011fr
dc.date.issued2011fr
dc.identifier.isbn9780494896570fr
dc.identifier.urihttp://hdl.handle.net/11143/5810
dc.description.abstractTelomeres play an important role in carcinogenesis. They assure immortalization of tumor cells by maintaining their length through the activation of telomerase or the alternative lengthening of telomere. Despite these mechanisms, telomeres of tumor cells are generally shorter than those of normal cells. In cancer cells, short telomeres promote chromosomal instability, which is one of the aggravating factors of neoplastic process. Also, the nuclear architecture of telomeres can be altered during carcinogenesis and cause genomic instability. To further understand the roles of telomeres in cancer, we studied the length of individual telomeres and their nuclear architecture in neoplastic cells. Using chronic myeloid leukemia (CML) as a model, we established the first length profile of all individual telomeres in cancer. We found that telomeres on chromosome arms Xp, 18p and 5p were among the longest while the shortest were on 21p and 21q . Also, by comparing with normal cells, we established that individual telomeres of CML cells had different shortening rates. Moreover, we noted the presence of long telomeres on some specific chromosome arms in CML cells. These data led us to explore different mechanisms of telomere length maintenance in CML cells and we showed that both telomerase and the ALT can be used to maintain their telomere length. Finally, the use of LoVo cell line, from colon carcinoma, allowed us to show that the profile of individual telomere length can be dissimilar in different cancers; and specific mutations of TP53 influence this profile in a same cancer cell. Therefore, the profile of individual telomere length of a cancer cell is defined by the genetic background of the individual, the tumor type, and the nature of the mutations. The study of nuclear architecture of telomeres was done in three different settings. First, we explored impacts on nuclear architecture of telomeres after exposing normal cells to DNA-damaging agents. We particularly observed the presence of telomeric aggregates and a change in the position of telomeres in response to UVB exposure. Next, we showed that remodeling of the nuclear architecture of telomeres could occur as early as the first clinical phase of CML. Moreover, we categorized CML cells into two groups according to the number of telomeric aggregates. Finally, we showed that the mutation TP53-R175H lead to greater alteration of the nuclear organization of telomeres and a genomic instability than the other studied TP53 mutations. The work, presented here, fosters our understanding on the involvement of telomeres in carcinogenesis and will serve as foundation for future studies on length of individual telomeres and their nuclear architecture in cancers.fr
dc.language.isofrefr
dc.publisherUniversité de Sherbrookefr
dc.rights© Oumar Samassékoufr
dc.subjectGènes du capuchon télomériquefr
dc.subjectInstabilité génomiquefr
dc.subjectDommages télomériquesfr
dc.subjectTP53fr
dc.subjectLeucémie myéloïde chroniquefr
dc.subjectArchitecture nucléaire des télomèresfr
dc.subjectLongueur des télomères individuelsfr
dc.titleDynamique des changements de la longueur des télomères individuels et de leur architecture nucléaire dans les cellules néoplasiquesfr
dc.typeThèsefr
tme.degree.disciplineBiochimiefr
tme.degree.grantorFaculté de médecine et des sciences de la santéfr
tme.degree.levelDoctoratfr
tme.degree.namePh.D.fr


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