Tesi sul tema "Cancer du sein – Génétique"
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Bonadona, Valérie. "Le cancer du sein de survenue précoce : aspects cliniques, épidémiologiques et génétiques à partir d'une étude prospective dans le Rhône". Lyon 1, 2005. http://www.theses.fr/2005LYO10191.
Testo completoFabbro, Michel. "Apport de la biologie moléculaire à l'épidémiologie génétique du cancer du sein". Montpellier 1, 1991. http://www.theses.fr/1991MON11083.
Testo completoDucy, Mandy. "Caractérisation fonctionnelle de variations génétiques dans PALB2, un gène de susceptibilité au cancer du sein". Doctoral thesis, Université Laval, 2019. http://hdl.handle.net/20.500.11794/35287.
Testo completoHamdi, Yosr. "Evaluation of the association between common genetic variants and breast cancer risk". Doctoral thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/28384.
Testo completoBreast cancer is the most common malignancy in women. A set of environmental and genetic factors are involved in this complex disease. This project focused on the genetic components of breast cancer susceptibility and breast cancer risk modification in BRCA1 and BRCA2 mutation carriers. Currently, about half of the inherited susceptibility to breast cancer can be imputed to a combination of high-, intermediate-, and low-risk alleles. Thus, many as yet unknown susceptibility loci remain to be identified. Moreover, recent studies have provided evidence for the involvement of genetic risk factors that might considerably modify the risk of developing breast cancer in BRCA1 and BRCA2 mutation carriers. Furthermore, genome-wide association studies have shown that several genetic variants within non-coding gene regions are associated with breast cancer risk. In this project, we focused on regulatory gene variants and their association with breast cancer risk. The project was divided in two parts. In the first section, we evaluated the direct association between single-nucleotide polymorphisms associated with differential allelic expression and breast cancer risk in order to identify new loci of breast cancer susceptibility. In the second part, we evaluated the functional impact on gene expression of variants identified within the promoter regions of selected candidate genes and then, characterize the functional impact of these variants. In summary, the first part of this project has led to the identification of a new low-penetrance locus associated with breast cancer risk on the 4q21 locus (rs11099601; odds ratio=1.05, p= 6.4 x 10-6), and two new modifiers of breast cancer risk in BRCA1 mutations carriers (11q22.3 locus and the wild type allele of BRCA1). The second part of the project allowed us to describe new functional variants within the promoters of the selected breast cancer gene candidates. Other association studies in larger cohorts and further functional analysis will be required to confirm these results, which will allow their inclusion in breast cancer risk prediction tools and thus ensure a more accurate estimation of breast cancer risk.
Stieber, Daniel. "Analyse génétique de la sensibilité au cancer mammaire". Doctoral thesis, Universite Libre de Bruxelles, 2005. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/211000.
Testo completoFleury-Ricordeau, Laurence. "Modifications épigénétiques dans le cancer du sein". Toulouse 3, 2008. http://thesesups.ups-tlse.fr/301/.
Testo completoIn breast cancer, approximately one third of tumors express neither the estrogen receptor (ERa) nor estrogen regulated genes such as the Progesterone Receptor gene (PR). Our study provides new insights into the mechanism allowing hormone-activated expression of ERa target genes silenced in ERa-negative mammary tumor cells. In cell lines derived from ERa-negative MDA-MB231 cells, stable expression of different levels of ERa from a transgene did not result in transcription of PR. A quantitative comparative analysis demonstrates that inhibiting DNA methyltransferases using 5-aza-2'-deoxycytidine or specific disruption of DNMT1 by small interfering RNAs and treatment with the histone-deacetylase inhibitor Trichostatin A enabled ERa-mediated hormone-dependent expression of endogenous PR. We show that demethylation of a CpG island located in the first exon of PR was a prerequisite for ERa binding to these regulatory sequences. Although not a general requirement, DNA demethylation is also necessary for derepression of a subset of ERa target genes involved in tumorigenesis. PR transcription did not subsist four days after removal of the DNA methyltransferase blocking agents, suggesting that hormone-induced expression of ERa target genes in ERa-negative tumor cells is transient. Our observations support a model where an epigenetic mark confers stable silencing by precluding ERa access to promoters
Sabatier-Montiel, Danièle. "Amplification et surexpression de certains gènes associés à la cancerogénèse mammaire : étude de 148 cas de cancer du sein traités au C.R.L.C. Val d'Aurelle de 1988 à 1991". Montpellier 1, 1993. http://www.theses.fr/1993MON11200.
Testo completoEnnour-Idrissi, Kaoutar. "Associations entre la longueur des télomères et les facteurs pronostiques du cancer du sein". Master's thesis, Université Laval, 2016. http://hdl.handle.net/20.500.11794/27561.
Testo completoTelomeres are highly specialized structures capping the ends of chromosomes that ensure genome integrity during replication. As telomere length is an indicator of cell aging, telomere shortening has been linked to aging-related diseases, especially cancer. Several studies suggest that lifestyle factors, which are modifiable factors and have been associated with breast cancer prognosis, have an impact on telomere length and that telomere length may be associated with breast cancer prognosis. The present project objective was to investigate the association of telomeres with traditional and potential breast cancer prognostic factors. First, a systematic review was conducted to evaluate the current state of knowledge concerning the value of telomere length as a prognostic factor. This systematic review identified important methodological differences that could account for the overall inconclusive results of previous studies and highlighted the potential value of telomere length as a breast cancer prognostic marker. A cross-sectional exploratory study was then performed to examine the association of peripheral white blood cells telomere length with traditional and potential prognostic factors among 162 breast cancer patients consecutively recruited at the « Centre des maladies du sein Deschênes-Fabia » in Quebec City. This study identified a positive association between specific domains of physical activity and telomere length in peripheral white blood cells. Even though an association of telomere length with traditional breast cancer prognostic factors was not identified, the value of telomere length as a breast cancer prognostic marker deserves to be explored through an unbiased longitudinal survival study.
Bencheikh, Meryem. "Pertes d'hétérozygotie dans les cancers du sein : incidence et corrélations avec d'autres altérations génomiques". Montpellier 2, 1992. http://www.theses.fr/1992MON20065.
Testo completoPlourde, Marie. "Identification et caractérisation des variants de séquences des gènes HSD17B1, HSD17B2, HSD17B7 et HSD17B12 chez des femmes atteintes d'un cancer du sein et possédant une forte histoire familiale de cancer du sein et de l'ovaire". Doctoral thesis, Université Laval, 2008. http://hdl.handle.net/20.500.11794/20495.
Testo completoTheillet, Charles. "Anomalies génomiques dans le cancer du sein". Montpellier 2, 1990. http://www.theses.fr/1990MON20062.
Testo completoPouliot, Marie-Christine. "Caractérisation de la signature transcriptionnelle chez des femmes québécoises avec une histoire familiale de cancer du sein". Master's thesis, Université Laval, 2016. http://hdl.handle.net/20.500.11794/27355.
Testo completoIn Canada, 5 to 10% of breast cancer cases are inherited and come from high-risk families. However, the majority of hereditary breast cancer is not yet characterized. Alternative splicing (AS) is a mechanism known to be involved in cancer development. The analysis of transcriptome in high-risk breast cancer individuals affected with breast cancer or not could reveal transcripts implicated in breast cancer susceptibility and development. RNA-seq technology was used to characterize the transcriptome in French Canadian families with high risk of breast and ovarian cancer. RNA extracted from immortalized lymphoblastoid cell lines of 117 women (affected or unaffected) and issued from BRCA1, BRCA2 or non-BRCA1/2 (BRCAX) families was used. Anova and Bonferroni tests followed by Scheffé test were performed to detect significantly and differentially expressed transcripts within these groups. In total, 95 transcripts corresponding to 85 genes were significant (p-value < 0.01). Hierarchical clustering based on transcriptional data allowed distinctive subgrouping of BRCA1/2 subgroups from BRCAX individuals. Enrichment in signaling pathways such as EIF2, IL-3 and mTOR was obtained. Furthermore, 28 transcripts were differentially expressed between BRCAX affected and unaffected women. The identification of differentially expressed transcripts could allow identifying individuals with a high susceptibility for breast cancer.
Lapointe, Julie. "Communication intrafamiliale de l'information génétique chez les personnes testées pour une susceptibilité au cancer du sein liée aux gènes BRCA1/2". Thesis, Université Laval, 2012. http://www.theses.ulaval.ca/2012/29508/29508.pdf.
Testo completoBanneau, Guillaume. "Étude génomique des formes familiales de cancer du sein". Thesis, Bordeaux 2, 2009. http://www.theses.fr/2009BOR21674.
Testo completoThe discovery of the BRCA1 and BRCA2 genes, along with their germline alterations in familial forms of breast cancer, led to the recognition of hereditary cancer predisposition syndromes in clinical practice (5% of cases). However, a deleterious alteration in one of these genes is not detected in approximately 30% of cases. To date, the underlying genetic cause of more than half of clinically suspected hereditary breast cancer predisposition remains unidentified despite the fact that several other genes have been associated with an increased risk of breast cancer (TP53, PTEN, FGFR2), demonstrating that there is significant genetic heterogeneity in this form of cancer. Transcriptomic and genomic profiles linked to BRCA1 or BRCA2 alterations have recently been identified and were used to predict (with a certain efficacy) if these genes are implicated in other breast cancers. It is therefore possible that other breast cancer predisposition genes (named BRCAx) could associate with breast cancer risk in transcriptomic and/or genomic profiles and characterise novel tumour endophenotypes. The project consists of a CGH-array and microarray study of 103 tumour samples from patients with clinically diagnosed familial breast cancer. Our results provide evidence of the existence of tumour subgroups with significantly different genomic profiles. In addition, we were able to establish a signature for BRCA1 tumours, another for BRCA2 tumours and a third signature for breast cancers resulting from Cowden syndrome
Gligorov, Joseph. "Polymorphismes et traitements néoadjuvants des cancers du sein : efficacité du docétaxel et polymorphisme d’ABCB1/MDR1". Paris 6, 2012. http://www.theses.fr/2012PA066082.
Testo completoIn non-metastatic breast cancer, neoadjuvant treatment allows to study the parameters influencing their effectiveness, related to the tumor and / or the host. The MDR family proteins, especially ABCB1 are involved in the mechanisms of resistance to anthracyclines and taxanes. The correlations between efficiency (histological response), ABCB1 polymorphism (patients and tumors) and pharmacokinetics of doxorubicin and docetaxel have been studied in the context of a therapeutic trial. In this study, polymorphism in exon 26 of ABCB1 (rs1045642) is the only that influences the pharmacokinetics of docetaxel and this only in premenopausal patients. Patients carrying CC genotype (40%) have an average value of the AUC of docetaxel significantly lower than those carrying genotypes CT (45%) and TT (15%) (p <0. 0001). Moreover it was found in premenopausal patients a statistically significant correlation between low rates of docetaxel AUC and diplotype 2677GG-3435CC and 1236CC haplotype-61AA-2677GG-3435CC. It has not been found a link between ABCB1 polymorphisms and the pharmacokinetics of doxorubicin. There is also a negative relationship between AUC of docetaxel and pathological response. There seems therefore that a minimum value of AUC of docetaxel is necessary to obtain a response. Furthermore, we found an association between tumor response and polymorphism of ABCB1 (C3435T genotype, CT and TT vs. CC)
Furrer, Daniela. "The human epidermal growth factor receptor 2 (HER2) in the breast cancer : from measurement to targeted treatment". Doctoral thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/37361.
Testo completoThe overexpression of the human epidermal growth factor receptor 2 (HER2) and/or HER2 gene amplification are predictive factors in breast cancer. Following the HER2-targeted treatment with trastuzumab, the reliable evaluation of HER2 has become essential. Unfortunately, up to 50% of HER2-positive breast cancer patients develop resistance towards this drug. The objectives were: 1). To determine the most reliable and economical method to evaluate HER2 status (cohort of 521 consecutive breast cancer cases); 2). To examine the association between tobacco and alcohol consumption, and two HER2 polymorphisms (Ile655Val and Ala1170Pro), and the response to trastuzumab (cohort of 236 HER2-positive breast cancer patients treated with trastuzumab). Moreover, in a pilot study, we explored the association between genome-wide DNA methylation patterns in breast cancer tissues and the response to trastuzumab (cohort of 12 breast cancer patients treated with trastuzumab). HER2 status was evaluated by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and TaqMan assay. We compared HER2 status determined by FISH on whole tissue (WT, one tissue per slide) section and tissue microarray (TMA, 60 tissues per slide) section, and HER2 status evaluated by IHC and FISH on the block used for diagnostic (diagnostic block) and on a randomly chosen additional block (random block). Clinicopathological information were assessed by review of medical records, tobacco and alcohol consumption by an administered validated questionnaire. DNA methylation patterns were evaluated using the Illumina Infinium HumanMethylation450 BeadChip. Overall concordance between HER2 status determined by FISH on WT and TMA sections was 98.2% and that between diagnostic and random blocks was 98.0% for FISH and 93.6% for IHC. Tobacco consumption and the Val allele were associated with a worse response, whereas alcohol consumption was associated with a better response. Methylation pattern in tumor tissues of HER2-positive breast cancer patients who acquired resistance to trastuzumab treatment differed from that of HER2-positive breast cancer patients who responded to trastuzumab treatment. However, this observation seemed to depend upon the method of bioinformatics analysis used. We conclude that FISH performed on TMA section represents a reliable and economical method for the evaluation of HER2. Results obtained by FISH, but not those obtained by IHC, fulfill the recommendations of the College of American Pathologists of concordance greater than 95% between the reference method and the new method. Tobacco use, alcohol consumption and Ile655Val HER2 polymorphism might influence the response to trastuzumab treatment.
Côme, Christophe. "Fonction des facteurs de transcription de la famille snail dans les cancers du sein et du côlon". Montpellier 2, 2005. http://www.theses.fr/2005MON20197.
Testo completoHaensler, Patrick. "Cancer du sein chez l'homme (caractéristiques épidémiologiques, cliniques, thérapeutiques et génétiques à partir de 40 cas traités au C. R. L. C. De Montpellier)". Montpellier 1, 1996. http://www.theses.fr/1996MON11083.
Testo completoTessereau, Chloé. "Le macrosatellite RNU2 : caractérisation, évolution et lien avec la prédisposition génétique au cancer du sein". Phd thesis, Université Claude Bernard - Lyon I, 2014. http://tel.archives-ouvertes.fr/tel-01058217.
Testo completoTreilleux, Isabelle. "Cancer du sein et oestrogènes : régulation de l'expression du récepteur aux oestrogènes humain". Lyon 1, 1997. http://www.theses.fr/1997LYO1T161.
Testo completoSlim, Ferial Amira. "Une isoforme de Allograft Inflammatory Factor-1 (AIF1) impliquée dans le cancer du sein". Master's thesis, Université Laval, 2018. http://hdl.handle.net/20.500.11794/34495.
Testo completoBreast cancer (BC) represents one of the most common and dangerous cancers in terms of mortality and incidence among women worldwide. It is even more recurrent in developed countries including Canada [2]. BC is a complex and multifactorial disorder, its severity and response to treatment differs from case to case and its diagnosis can be tricky due to the heterogeneity of the pathology. Thus, this project aims to study a potential BC risk factor that can be used for diagnosis and treatment of BC patients. Allograft Inflammatory Factor-1 (AIF1) is a protein involved in many inflammatory diseases that has also been associated with cancer, however, in most studies, only one isoform has been analyzed. Our analyses of the transcriptional profile of individuals from French Canadian families with high risk of BC (BRCA1/BRCA2 or not-BRCA1/2 (BRCAX)) identified significantly and differentially expressed transcripts between the different groups. Among them, two AIF1 splice variants were highly overexpressed in the BRCAX lymphoblastoid cell lines (LCLs) of the affected sister comparatively with her non-affected sister. Our gene expression analysis revealed that both isoforms were mostly expressed in the least aggressive BC and this expression resulted from the tumor microenvironment, AIF1v1 being mostly expressed by lymphocytes and AIF1v3 by activated macrophages. We also demonstrated the effect of docosahexaenoic omega-3 fatty acids (DHA) on the downregulation of AIF1 isoforms expression in BRCAX LCLs. Lastly, our data showed that AIF1 isoforms expression in breast tumors and breast adipose tissue correlated with metabolic and clinical parameters of BC patients. Ultimately, all data and information resulting from this study represent a major breakthrough for the scientific community and the cancer research field since it is the first study on AIF1v1 and its involvement in BC, breast tumor microenvironment and inflammatory reaction.
Curtit, Elsa. "Rôle des déterminants génétiques constitutionnels dans le cancer du sein". Thesis, Bourgogne Franche-Comté, 2017. http://www.theses.fr/2017UBFCE017.
Testo completoAs in any disease, the development of breast cancer depends on genetic hereditary factors and environmental acquired factors. Genetic factors of breast cancer involve rare pathogenic mutations with high risk of developing a breast cancer and frequent genetic variants (single nucleotides polymorphisms - SNP) responsible for a low increase in the risk of cancer. The works presented in this manuscript show that germline genetic factors strongly determine the risk of developing a breast cancer, but also the subtype of breast cancer and may impact the prognosis. Estrogen-positive, HER2-negative breast cancer development is associated with 4 intronic SNP in FGFR2 gene. Breast cancer prognosis is not associated with variants conferring a risk of developing a breast cancer. Four independent SNP are associated with bad outcomes in triple-negative breast cancers.The way that leads from patient genome to tumor genome is complex, mainly unknown and probably different for each case, as illustrated in the two case reports involving BRCA1/2 germline mutations described in the second part of the manuscript. Last work is a clinical research trial and shows a prevalence of BRCA1/2 mutations of around 3%, in a prospective cohort with metastatic breast cancer patients unselected on their age, cancer type or family history
Lecarpentier, Julie. "Étude des facteurs modificateurs du risque de cancer du sein des femmes à risque génétique élevé". Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00910388.
Testo completoLaffargue-Carrère, Nathalie. "Applications de la technique PCR à l'étude quantitative et qualitative de gènes impliqués dans la tumorogénèse mammaire". Bordeaux 2, 1996. http://www.theses.fr/1996BOR28470.
Testo completoTournier, Isabelle. "Mécanismes d'inactivation des gènes impliqués dans les deux formes majeures de prédisposition héréditaire aux cancers : la prédisposition aux cancers du sein et de l'ovaire et le cancer colorectal héréditaire non polyposique (HNPCC) ou syndrome de Lynch". Rouen, 2007. http://www.theses.fr/2007ROUE04NR.
Testo completoBouchard, Karine. "Comportements de santé et détresse psychologique des femmes s'engageant dans le processus d'un test génétique de prédisposition au cancer du sein BRCA1/2". Thesis, Université Laval, 2007. http://www.theses.ulaval.ca/2007/24262/24262.pdf.
Testo completoFranco, Noreli. "Rôle de l'instabilité génomique dans la tumorigenèse mammaire et la réponse à la chimiothérapie du cancer du sein". Dijon, 2002. http://www.theses.fr/2002DIJOS002.
Testo completoVallée, Marie-Hélène. "Effet de la publication des résultats de l'étude de la Women's Health Initiative sur l'utilisation de l'hormonothérapie de remplacement par les femmes testées pour une prédisposition génétique au cancer du sein". Thesis, Université Laval, 2006. http://www.theses.ulaval.ca/2006/23866/23866.pdf.
Testo completoBertin, Nicolas. "Expression des thrombospondines 1 et 2 dans la glande mammaire normale et en pathologie : corrélation avec les facteurs pronostiques classiques et l'angiogenèse : utilisation de l'amplification compétitive". Lyon 1, 1997. http://www.theses.fr/1997LYO1T006.
Testo completoBellucci, Luca. "The role of histone variant H2A. Z in the regulation of gene expression in breast cancer cells". Toulouse 3, 2013. http://thesesups.ups-tlse.fr/1939/.
Testo completoDuring my PhD, I studied the mechanisms of regulation of gene expression in breast cancer. In particular, I was interested in the epigenetic regulation of p21 gene expression in an estrogen receptor negative breast cancer cells (MDA-MB231 cells). We found that in these cells a TSA treatment stimulated p21 expression and increased acetylation of H2A. Z present at the p21 promoter. H2A. Z was strongly associated with the transcription start site of p21. Moreover, depleting the cellular pool of H2A. Z compromised p21 activation and response to HDACi. Acetylation of H2A. Z rather than its association of regulatory element per se was important for p21 expression. My studies led to a publication (Bellucci et al. , 2013 [1]) which shows that p21 gene activation in MDA-MB231 cells is p53-independent and controlled by the H2A. Z histone variant and its acetylation. Normally, activation of p21 expression can be p53-independent or dependent, according to the cell system used. But the mechanism behind p21 activation, via HDACi, remains poorly understood. Moreover, p21 regulation depends on the binding of the histone variant H2A. Z. Using the Cyclin D1 gene as a model, I also participated in a project, which shows how, in this case too, H2A. Z acetylation is critical for gene regulation in estrogen receptor positive and negative breast cancer cells. We identified the enzymes involved in H2A. Z acetylation (Tip60) and in chromatin remodeling (Tip48), to propose a model for transcription activation of this gene
Lemee, Fanny. "Dérégulation de l'expression des ADN polymérases translésionnelles, instabilité génétique et progression des cancers colorectaux et du sein". Toulouse 3, 2009. http://thesesups.ups-tlse.fr/604/.
Testo completoThe faithful maintenance of the genome is essential for the prevention of most of human solid cancers. Beside "replicative" DNA polymerases, a growing number of alternative mammalian DNA polymerases, called translesional (TLS), have been recently identified. These enzymes play specialized roles at the interplay of DNA replication, repair and recombination (the "3Rs") transactions, critical pathways to preserve the genome integrity. Our working hypothesis is that an unbalanced expression of replicative/TLS DNA polymerases can modify the replication program (the so-called "replicative stress"), and can therefore trigger genetic instability. Here, we show that the specialized Y-family TLS DNA polymerases Pol-kappa and Pol-eta are downregulated in colorectal tumor biopsies compared with adjacent normal tissues. With the aim to investigate the molecular bases underlying such defective expression, we carried out a genetic cartography of the promoters and found that they contain repressive as well as activating regions. We identified CREB and Sp1 as transcriptional activators of the POLK promoter, and we observed that a decreased level of these factors in colorectal biopsies correlated with Pol-kappa downregulation. These observations suggest that inhibition of CREB and Sp1 proteins could contribute to the reduced level of Pol-kappa in colorectal tumours. In a second part we report that the recently identified Pol-theta was the only specialized/TLS DNA polymerase significantly up-regulated in breast tumours. . .
Maillot, Gérard. "Contribution à l'étude de l'expression et des fonctions des microRNAs dans les cancers du sein". Toulouse 3, 2009. http://thesesups.ups-tlse.fr/616/.
Testo completoMicroRNAs are key players in post-transcriptional gene silencing. Altered expression and/or activity of microRNAs contribute to cancer development by modifying the expression of key cancer genes. Our work focused on the study of microRNAs expression and functions (i) in hormonal regulation and (ii) in metastatic progression of breast cancers. (i) We showed that upon activation of estrogen receptors (by 17-ß-estradiol), an important transcription factor , microRNAs expression are repressed in several estrogen-dependent breast cancer cell lines. This downregulation of microRNAs expresion is acting in part in the estrogen-dependent cell proliferation. (ii) In a mouse model of metastatic progression, we showed an important deregulation of microRNAs expression in regard with this progression. In particular, our work suggest that miR-31 and 125b would have prometastatic features
Ayme, Aurélie. "Prédispositions génétiques au cancer du sein et de l'ovaire dans la population suisse entre 1996 et 2009 : bilan de l'activité oncogénétique et du dépistage de mutations constitutionnelles dans les gènes BRCA1/BRCA2". Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM5081.
Testo completoGenetic predispositions are responsible for 5 to 10 % of all breast and ovarian cancers. The main breast/ovarian cancer predisposing genes are BRCA1 and BRCA2. For some years, the screening of pathogenic mutations in BRCA1/BRCA2 genes is provided in a clinical setting. At the Hôpitaux Universitaires de Genève (HUG, Geneva, Switzerland), a consultation in predictive oncology has been set up since 1994 for individuals concerned by the evaluation of their familial cancer risk and the probability to carry a genetic predisposition to cancer. Until 2009, the single national laboratory for BRCA1/BRCA2 testing was established in the HUG. The objectives of this work were to evaluate different aspects of the consultation process for breast/ovarian cancer predisposition syndromes provided in our Unit and to review all BRCA1/BRCA2 complete screenings (n=1’163) performed between 1996 and 2009. Results of the present study will certainly influence future activity in predictive oncology, particularly regarding the role of the genetic counselor
Nugoli, Mélanie. "Instabilité génétique des cancers du sein et étude à haute résolution des anomalies quantitatives du bras long du chromosome 1 (1q)". Montpellier 2, 2003. http://www.theses.fr/2003MON20116.
Testo completoAlbert, Hélène Marie. "Epissage alternatif des phosphatases CDC25 dans le cancer du sein : expression des différents variants dans des modèles cellulaires et tissulaires de cancer mammaire et régulation en conditions de stress génotoxique". Thesis, Metz, 2011. http://www.theses.fr/2011METZ025S/document.
Testo completoCDC25 phosphatases play an important role in cell cycle progression. Moreover, an overexpression of CDC25 was reported in numerous cancers, particularly in breast cancer, and is often correlated with a poor prognosis. CDC25 are represented by three isoforms: A, B and C encoded by distinct genes, all three submitted to an alternative splicing mechanism. Few studies suggested that some CDC25 splicing variants could be more involved in cancers than others, but no such study has so far been conducted in breast cancer.The first aspect of this study, referred to clinic, consists in the evaluation of different CDC25 splicing variants proportion in breast cancer, from the perspective of developing a new prognostic tool. This study was performed on two models. On the one hand, several mammary cancerous cell lines were characterized concerning CDC25 variants expression thanks to the development of a novel quantitative RT-PCR method. Interestingly, we observed an overexpression of A2 and B2 transcripts and an increase of C5/C1 ratio in multidrug resistant cell lines, suggesting a link between the expression of these variants and the resistance phenotype. On the other hand, this study was extended to the determination of CDC25 variants expression in mammary tumoral tissues in comparison to that of matched peritumoral tissues. Quantitative PCR results obtained for the 75 pairs of tissues tested showed an overexpression of CDC25A in 64% of tumors, mainly due to A1 variant (69%); of CDC25B in 55% of tumors, partially linked to B1 and B2 variants expression (47% and 21% respectively); and of CDC25C in 75% of tumors, the C5 variant being clearly more involved than C1 (overexpression in 86% and 43% respectively). We have finally established correlations between CDC25 transcripts expression and some tumor characteristics, as the tumor grade and a lack of estrogens receptors for CDC25A and CDC25B and the tumor size for CDC25C.The second part of this project consists in a mechanistic study regarding the regulation of CDC25 splicing in DNA damage conditions. The treatment of several breast cancer cell lines with different genotoxic agents (doxorubicin, camptothecin, etoposide, cisplatin and tert-butyl hydroperoxide) induces a modification of CDC25C splicing profile, consisting in a large increase in C5 variant proportion compared to that of C1 (both at mRNA and protein levels). This regulation occurs during the early response to DNA damage, before the onset of apoptosis and is associated with a cell cycle arrest. We have also shown that this modulation of CDC25C splicing is dependent of ATM/ATR kinases and independent of p53. Finally, these results allowed to highlight an additional regulation pathway in the cellular response to genotoxic stress in breast cancer cells
Cornen, Stéphanie. "Caractérisation moléculaire des cancers du sein luminaux B". Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM5040.
Testo completoBreast cancers (BCs) of the luminal B subtype have a poor prognosis. To better understand this subtype we studied in 188 BCs of various molecular subtypes, DNA copy number aberrations, DNA promoter methylation, gene expression profiles, and somatic mutations in nine selected genes. A total of 237 and 101 luminal B-specific candidate oncogenes and tumor suppressor genes (TSGs) presented a deregulated expression in relation with their CNAs. Interestingly, 88% of the potential TSGs are located within chromosome arm 6q. 101 candidate oncogenes were validated in a public series of 5,765 BCs and the overexpression of 67 was associated with poor survival in luminal tumors. 24 genes presented a deregulated expression in relation with a high DNA methylation level. FOXO3, PIK3CA and TP53 were the most frequent mutated genes among the nine tested. In a meta-analysis of next-generation sequencing data in 875 BCs, PIK3CA, TP53 and GATA3 were the most frequent mutated genes. Numerous molecular alterations targeted common signalling pathway, included 3 ways wich may play a major in the luminal B subtype: TP53 pathway and chromosomal instability, PI3K/AKT/MTOR/FOXO and MAPK/JNK pathway, and epigenomic and transcription factors alterations. In conclusion, we have reported a repertoire of luminal B candidate genes that may be involved in the development and/or hormone resistance of this subtype
Sévilla, Christine. "Evaluation économique des innovations biomédicales : l'exemple de la diffusion des tests génétiques en oncologie". Paris, EHESS, 2003. http://www.theses.fr/2003EHES0045.
Testo completoThe localisation and the identification of two breast/ovarian cancer susceptibility genes, BRCA1 and BRCA2, have made it possible the introduction of genetic testing for predisposition to these cancers in new medical practices, intended for at risk persons identified on the basis of their idividual and familial characteristics. The objective of this work is to study the diffusion of this brand-new biomedical innovation and the difficulties it generates. After having presented the general factors of the diffusion of innovations identified by the economic theory, on the supply side and on the demand side, we present the problem posed by the genetic testing : we show how the diffusion of these tests poses some difficulties related to the general factors of diffusion or to problems more specific to activities of predictive medicine, but also how the resolution of some difficulties necessitates the adoption of a normative approach
Leblond, Débora. "Impact psychologique du test génétique de prédisposition aux cancers du sein et de l'ovaire chez les femmes atteintes d'un cancer du sein et initiant la recherche de mutation BRCA1/2 dans leur famille". Paris 5, 2011. http://www.theses.fr/2011PA05H110.
Testo completoObjectives This research’s objectives are to measure the cognitive, emotional, functional and behavioral impact of genetic screening for BRCA1/2, and its predictors, for women initiating the search for mutation in their family. A particular interest was paid to accuracy between subjective and objective risk, as well as on the place of the fear of recurrence (FRC) and the communication of an inconclusive result, for these consultants affected by breast cancer. Method The psychological impact of the test was measured by questionnaires after the first consultation (T1) and after the test result (T2). On 289 eligible patients, 243 sent back these questionnaires at T1 and 180 participated at both assessment time. Results Half of the women have inaccurate perception of their risk of predisposition at T1. Finally, the psychological impact of genetic testing is less beneficial than hypothesized, on the emotional and functional levels, and seems to be connected to the PRC or its associated factors. The impact of the inconclusive result differs significantly slightly from other results. It neither results in false reassurance nor modifies screening intentions, mainly predicted by geneticists’s recommendations. However, level of traitanxiety and ways of coping with cancer can modify the impact of test results. Conclusion If the psychological impact of genetic screening for BRCA1/2 remains acceptable, it is nevertheless advisable not to neglect its effect on consultants already affected by breast cancer, who have to face their risk of recurrence
Lemaçon, Audrey. "Développement d'outils bioinformatiques et de méthodologies d'apprentissage machine pour une meilleure compréhension des éléments génétiques sous-jacents à la susceptibilité au cancer du sein". Doctoral thesis, Université Laval, 2019. http://hdl.handle.net/20.500.11794/35418.
Testo completoBreast cancer is one of the leading causes of death from cancer among Canadian women (about 1 in 8 Canadian women will develop breast cancer during her lifetime and 1 in 31 will die from the disease). Evidence suggests that most breast cancer cases develop in a small proportion of women with a genetic susceptibility to the disease. Since the personalized assessment of this risk is based on the certainty that women can be divided into several groups according to their inherent genetic risk, it is essential to identify the actors responsible for this genetic susceptibility to breast cancer in order to offer these at-risk women, personalized preventive measures. Thus, since the discovery of the associated genes BRCA1 in 1994 and BRCA2 in 1995, tremendous efforts have been made to identify the genetic components underlying breast cancer risk and many other deleterious mutations have been uncovered in susceptibility genes such as PTEN, PALB2 or CHEK2. Unfortunately, despite these efforts, the susceptibility genes/loci known to date only explain about half of the genetic risk associated with this disease. Acknowledging the challenges, many international groups have partnered in consortia such as the Breast Cancer Consortium (BCAC) or the Consortium of Investigators of Modiers of BRCA1/2 (CIMBA) to join their resources for the identication of what has been called breast cancer "missing heritability". Several hypotheses have been formulated as to the sources of this missing heritability and, among these hypotheses, we have explored two. First, we tested the hypothesis of many common low penetrance genetic variants still to be discovered through a large genome-wide association study conducted within the OncoArray Network. In a second step, we tested the hypothesis according to which rarer variants of higher penetrance, could be discovered in the coding regions of the genome, through the evaluation of the predictive power of these variants by an innovative approach of exomes data analysis. Thus, we were able to demonstrate the veracity of the rst hypothesis by the discovery of 65 new loci associated with overall breast cancer susceptibility. In addition, these studies having highlighted the need for assistance tools for prioritization analysis, we developed two softwares to help prioritize human genetic variants. Finally, we developed a new multi-step methodology, combining the analysis of genotypes and haplotypes in order to assess the predictive power of coding variants. This approach, taking advantage of the power of machine learning, enabled the identication of new credible coding markers (variants alone or combined into haplotypes), signicantly associated with the phenotype. For susceptibility loci as well as for candidate genes identied during the analysis of exome data, it will be essential to conrm their involvement and effect size on large external sample sets and then perform their functional characterization. If they are validated, their integration into current risk prediction tools could help promote early management and well-calibrated therapeutic interventions for at-risk women.
Le, Dily François. "Interrelations entre le récepteur alpha des œstrogènes et le récepteur nucléaire coup-tfi dans le contrôle de la prolifération et de la différenciation de cellules mammaires". Rennes 1, 2006. http://www.theses.fr/2006REN1S090.
Testo completoOliva, Vilana Joan. "Antioestrogènes et cancer du sein : Modulation de l'expression de gènes au cours de l'acquisition de la résistance à l'hydroxytamoxifène". Montpellier 2, 2005. http://www.theses.fr/2005MON20006.
Testo completoPuget, Nadine. "Prédisposition génétique au cancer du sein : recherche de mutations dans les régions régulatrices et de réarrangements structuraux du gène BRCA1". Lyon 1, 1999. http://www.theses.fr/1999LYO1T093.
Testo completoPerrin-Vidoz, Laure. "Étude de la dégradation des ARN messagers porteurs d'un codon de terminaison prématuré : implication dans la prédisposition génétique au cancer du sein et de l'ovaire chez les patients porteurs de mutations germinales du gène BRCA1". Lyon 1, 2003. http://www.theses.fr/2003LYO10038.
Testo completoZhang, Bo. "Structure and biological function of human 3-alpha hydroxysteroid dehydrogenase type 3 in breast cancer". Thesis, Université Laval, 2014. http://www.theses.ulaval.ca/2014/30451/30451.pdf.
Testo completoHuman 3-alpha hydroxysteroid dehydrogenase type 3 (3α-HSD3) has an essential role in the inactivation of androgen 5α-dihydrotestosterone (5α-DHT). By a combination of mutagenesis, kinetics and X-ray crystallography, we demonstrate that the mutation of Valine54 to Leucine54 in 3α-HSD3 reduces its 5α-DHT inactivation ability and enhances a 20-alpha hydroxysteroid dehydrogenase activity. Furthermore, the crystal structure of 3α-HSD3 in complex with 5α-androstane-3,17-dione/epi-androsterone (A-dione/epi-ADT) is obtained by co-crystallization with 5α-DHT, which implies that 5α-DHT has the alternative binding mode within 3α-HSD3. Suppression of 3α-HSD3 expression by specific siRNA not only increases 5α-DHT concentration in MCF7 cells, but also decreases MCF7 cell proliferation in the presence of 5α-DHT. Estrogen receptor alpha (ERα) controls sexual development and reproductive functions. We establish a purification protocol of ERα fragment including its DNA binding domain and ligand binding domain (DBD-LBD). Preliminary crystallogenesis of ERα DBD-LBD in complex with estrogen response elements is carried out. Additionally, we report a simple and efficient purification method for ERα LBD.
Margueron, Raphaël. "Acétylation et signalisation oestrogénique dans les lignées de cancer du sein". Montpellier 1, 2003. http://www.theses.fr/2003MON1T009.
Testo completoFreund, Ariane. "Rôle de l'Interleukine-8 (IL-8) et contrôle de son expression dans les cellules de cancer du sein". Montpellier 1, 2004. http://www.theses.fr/2004MON1T003.
Testo completoFortin, Jessyka. "Analyse génomique et transcriptionnelle des gènes de susceptibilité aux cancers du sein et de l'ovaire BRCA1 et BRCA2 chez les Canadiennes françaises". Thesis, Université Laval, 2005. http://www.theses.ulaval.ca/2005/23063/23063.pdf.
Testo completoThe discovery of two genes, BRCA1 and BRCA2, which, when altered, confer markedly increased susceptibility to breast and ovarian cancer, has facilitated the identification of individuals at particularly high-risk of these diseases. First, extensive screening for germline mutations in the French-Canadian high risk breast/ovarian cancer families led to the detection of the first BRCA1 splice variant caused by an in-frame insertion. This transcript, designated exon 13A, is generated by an insertion of 66 nucleotides between exon 13 and 14, due to an alternative splicing of parts of intron 13 (IVS13-2786_-2720). Second, based on our current extensive analysis, without using PCR-based methods, there is no evidence supporting the existence of any deleterious BRCA1/2 recurrent genomic rearrangement in these same French-Canadian breast/ovarian cancer families.
Muller, Etienne. "Les défis du séquençage à haut débit dans l'exploration génétique des cancers du sein et de l'ovaire". Thesis, Normandie, 2017. http://www.theses.fr/2017NORMR100/document.
Testo completoBreast and ovarian cancers appear in 5 to 10% of cases in a context of genetic predisposition, of which only a small proportion is explained by the presence of a pathogenic variant on the BRCA1, BRCA2 and PALB2 genes. High throughput sequencing can explore this missing heredity, but represents a new challenge both in computing, statistics and biology. Three approaches using this new technology have been used to investigate new predisposition factors. First, the risks associated with 34 known or suspected genes involved in predispositions were estimated from the analysis of 5,131 index cases and the development of a new statistical approach. Also, the participation of mosaic neo-mutations in the syndrome was explored from 1,750 index cases from the previous study, with a software developed specifically for detecting poorly represented variants: outLyzer. Finally, the exploration by sequencing of the missing heredity was extended to a panel of 201 genes involved in cancer, from 118 patients selected for the early onset of their disease, a highly suggestive element of a predisposition factor. The results of this work validated the relevance of the PALB2, RAD51C and RAD51D study for patient management, and also suggested an underestimated involvement of mosaic variants. However, there are still very likely other highly penetrating genetic factors to be discovered, but whose risk modulation is based on an oligogenic model
Hamdi, Yosr. "Interactions entre les gènes des enzymes antioxydantes et leurs relations avec le cancer du sein". Thesis, Université Laval, 2008. http://www.theses.ulaval.ca/2008/25881/25881.pdf.
Testo completoVeyrier-Cammas, Anne. "Rôle et mode d'action du régulateur traductionnel hnRNP A1 dans les cellules tumorales mammaires". Toulouse 3, 2008. http://thesesups.ups-tlse.fr/335/.
Testo completoMRNA binding proteins or mRBPs are involved in the regulation, the coordination and the coupling of post-transcriptional gene expression. Modifications in the regulation of their expression and/or activity in cancer contribute to the tumoral development. Our work focused on the study of the translational regulator, hnRNP A1,. We have shown that the translational activity of hnRNP A1 is regulated by its cytoplasmic relocalization upon different stress conditions. We have also observed that a cytoplasmic localization of hnRNP A1 is associated with metastatic relapse and bad prognosis in breast tumors, and we have initiated a study of the effects of this cytoplasmic relocalization on tumorigenesis. This work suggests that regulation of translation by subcellular relocalization of an mRBP may be determinant in cancer