Dissertations / Theses on the topic 'BRCA genes'
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Mavaddat, Nasim. "Risk modelling in BRCA1 and BRCA2 mutation carriers." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610839.
Full textEwald, Ingrid Petroni. "Caracterização de um grupo de pacientes em risco para câncer de mama e ovário hereditários quanto a presença e frequência de rearranjos gênicos em BRCA." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/53154.
Full textBreast cancer is one of the most common malignancies affecting women worldwide. In Brazil, the State of Rio Grande do Sul has incidence rates and mortality from breast cancer are among the largest in the country. Approximately 5-10% of the cases are caused by germline mutations in predisposing genes including BRCA1 and BRCA2 are associated with the syndrome of breast and ovarian cancer Hereditary (Hereditary Breast and Ovarian Cancer Syndrome or HBOC, OMIM # 114480). The identification of inherited cases of breast cancer is important because affected individuals have cumulative risk life much higher than the population for developing cancer because of an affected family may also be at risk because there are measures of intensive screening and preventive interventions that can significantly decrease the risk of cancer in mutation carriers. The molecular diagnosis of HBOC syndrome is laborious and expensive due to the molecular heterogeneity of the disease. Families that have characteristics indicative of a cancer predisposition syndrome of hereditary breast and ovarian cancers, but are negative for mutations in BRCA1/2 have been tested for large rearrangements because these abnormalities have been identified as accounting for at least 10 % of all cases HBOC identifiable mutation, including large deletions or duplications. A recent study from Portugal, the founder showed that a rearrangement in exon 3 of BRCA2 occurs in 8% of HBOC families of the north. The objectives of this work included the verification of the frequency and characterization of gene rearrangements in BRCA1 and BRCA2 genes, including c.156_157insAlu founder mutation in exon 3 of BRCA2 mutations in Brazilian families at high risk for HBOC syndrome. In a group of 145 individuals at risk unrelated traced to c.156_157insAlu founder mutation in exon 3 of 3 found BRCA2 mutation carriers (prevalence 2%). In a group of 145 individuals at risk unrelated screened for gene rearrangements in BRCA1 and BRCA2 by the technique of MLPA (multiplex ligationdependent probe amplification) identified four carriers of germline mutation, and two of the mutation in a gene rearrangement in the gene BRCA1 (1.4%) involving Alu sequences. Gene rearrangements in BRCA1 and BRCA2 account for a portion of HBOC mutations in Brazilian families. This study, involving a large series of families with HBOC syndrome phenotype, no new rearrangements identified founders, however, showed the presence of rearrangements in both BRCA1 and BRCA2, reiterating the importance of active search for these changes, which hardly are identified by conventional techniques of gene sequencing. The technique of MLPA protocol associated with a specific mutation detection founder Portuguese c.156_157insAlu strategy can be used as initial screening for mutations in families with Brazilian syndrome. The results presented here, however, indicate mutations that will be identified in less than 10% of the cases using this strategy.
Ramirez, Christina J. "BRCA genes : conserved regions and the potential effect of missense changes /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/5052.
Full textTurk, Casey M. "Paralemmin splice variants and mRNA and protein expression in breast cancers." Connect to this title, 2008. http://scholarworks.umass.edu/theses/194/.
Full textWarren, Curtis R. "Linker region of the BRCA2 protein increases chemoresistance to cisplatin: Screen for the characterization of cancer-associated variants." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 84 p, 2009. http://proquest.umi.com/pqdweb?did=1885607671&sid=3&Fmt=2&clientId=8331&RQT=309&VName=PQD.
Full textSolyom, S. (Szilvia). "BRCA/Fanconi anemia pathway genes in hereditary predisposition to breast cancer." Doctoral thesis, Oulun yliopisto, 2011. http://urn.fi/urn:isbn:9789514294099.
Full textTiivistelmä BRCA1 ja BRCA2 ovat kaksi tärkeintä perinnöllisen rinta- ja munasarjasyövän alttiusgeeniä. Niissä esiintyvät ituradan muutokset selittävät kuitenkin vain noin 20 % familiaalisista rintasyöpätapauksista. Suurin osa alttiusgeeneistä on edelleen tunnistamatta ja näitä tekijöitä etsitään aktiivisesti. Tämän tutkimuksen tarkoituksena on ollut tunnistaa uusia alttiustekijöitä toisiinsa läheisesti liittyviltä BRCA/Fanconin anemia (FA) signaalinsiirtoreiteiltä. Viisi kandidaattigeeniä - MERIT40, ABRAXAS, BRIP1, CHK1 ja FANCA – kartoitettiin mutaatioiden suhteen suomalaisissa rintasyöpäperheissä käyttämällä konformaatiosensitiivistä geelielektroforeesia ja sekvensointia, tai multiplex ligation-dependent probe amplification- menetelmää. MERIT40-geenissä havaittiin useita aikaisemmin raportoimattomia nukleotidimuutoksia, mutta yhdenkään niistä ei havaittu liittyvän rintasyöpäalttiuteen. MERIT40-geenimuutosten mahdollista yhteyttä rintasyöpäalttiuteen ei ole tutkittu aikaisemmin. ABRAXAS-geenissä havaittiin missense-mutaatio (c.1082G>A, joka johtaa Arg361Gln aminohappokorvautumiseen) kolmessa pohjoissuomalaisessa rintasyöpäperheessä (3/125, 2.4 %). Muutosta ei havaittu terveissä kontrolleissa (N=867), ja ero mutaation esiintyvyydessä familiaalisten rintasyöpätapausten ja terveiden kontrollien välillä oli tilastollisesti merkitsevä (p=0.002). ABRAXAS c.1082G>A-muutos on todennäköisesti patogeeninen, sillä kyseinen aminohappopaikka on evolutiivisesti konservoitunut ja sijaitsee todennäköisellä tumaanohjaussignaalialueella. Funktionaaliset kokeet osoittivat, että mutatoitunut proteiinituote lokalisoitui villityypin proteiinia heikommin tumaan ja sen ohjautuminen DNA-vaurioalueille oli puutteellista. BRIP1- (FANCJ) ja CHK1-geeneistä etsittiin laajoja genomisia uudelleenjärjestelyjä, mutta niitä ei havaittu. Näin ollen kyseisillä muutoksilla ei ole merkittävää roolia perinnöllisessä rintasyöpäalttiudessa suomalaisessa väestössä. FANCA-geenissä havaittiin laaja heterotsygoottinen deleetio yhdessä tutkitusta 100 rintasyöpäperheestä. Deleetio poistaa geenin promoottorialueen lisäksi sen 12 ensimmäistä eksonia. Deleetioalleelia ei havaittu terveissä kontrolleissa, joten se mahdollisesti liittyy perinnölliseen rintasyöpäalttiuteen. Tutkimus on ensimmäinen, jossa raportoidaan laaja genominen deleetio FA-signaalinsiirtoreitin ylävirran geenissä familiaalisessa rintasyövässä
Mozersky, J. "'Ashkenazi mutations' and the BRCA genes : genetics, disease and Jewish identity." Thesis, University College London (University of London), 2009. http://discovery.ucl.ac.uk/19035/.
Full textSkoulidis, Ferdinandos. "Models of pancreatic carcinogenesis associated with inactivation of the BRCA2 breast cancer susceptibility gene." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609916.
Full textPRESNEAU, NADEGE. "Recherche de mutations constitutionnelles dans les genes de predispositions hereditaires aux cancers du sein et/ou de l'ovaire : brca-1, brca-2. recherche de nouveaux genes suppresseurs de tumeur impliques dans l'oncogenese mammaire." Clermont-Ferrand 2, 1999. http://www.theses.fr/1999CLF21122.
Full textFerlatte, Christy. "Patient preferences for an appropriate time for cancer genetic counseling and BRCA testing for women diagnosed with breast cancer." Waltham, Mass. : Brandeis University, 2009. http://dcoll.brandeis.edu/handle/10192/23193.
Full textOliveira, Sarah Franco Vieira de. "Caracterização da expressão de genes da via de reparo do DNA FA-BRCA e do gene MTAP em carcinomas mamários." reponame:Repositório Institucional da UFPR, 2013. http://hdl.handle.net/1884/33791.
Full textPaladini, L. "BIOLOGICAL SIGNIFICANCE OF ALTERATIONS IN BRCA1 AND BRCA2 GENES AND RESPONSE TO DNA DAMAGE AGENTS IN HEREDITARY BREAST CANCER." Doctoral thesis, Università degli Studi di Milano, 2017. http://hdl.handle.net/2434/488444.
Full textChan, Yuen-kwong. "Study on the role of genetic and epigenetic factors in relation to the BRCA genes in epithelial ovarian cancers." Click to view the E-thesis via HKUTO, 2002. http://sunzi.lib.hku.hk/hkuto/record/B42576726.
Full textBatista, Rui Pedro Monteiro. "Caracterização das mutações dos genes BRCA1 e BRCA2." Master's thesis, Universidade de Aveiro, 2012. http://hdl.handle.net/10773/10136.
Full textO cancro da mama é o tipo de neoplasia maligna mais incidente nas mulheres a nível mundial. Na maior parte dos casos tem origem esporádica, mas estima-se que cerca de 7% tem origem hereditária, relacionada com a herança genética de alguma mutação patogénica em genes de suscetibilidade para este cancro. A causa mais frequente de cancro hereditário da mama/ovário é a alteração de um dos genes BRCA (BRCA1 ou BRCA2). De fato as mutações germinativas destes genes são responsáveis por cerca de 50% dos casos de cancro hereditário da mama e/ou ovário. São ainda poucos os dados referentes ao perfil de mutações destes genes na população portuguesa, para além da descrição de uma mutação fundadora no gene BRCA2. Pretendeu-se com o presente estudo caracterizar, numa amostra de doentes portugueses com suspeita de cancro hereditário da mama/ovário, as mutações destes dois genes, avaliando os diferentes tipos de mutações encontradas, a prevalência de mutações comprovadamente patogénicas e, nomeadamente da mutação fundadora portuguesa. Pretendeu-se também testar o algoritmo de cálculo BRCAPro® no auxílio ao recrutamento para estudo genético de pacientes com suspeita de HBOC. Dos 121 casos estudados por DGGE/sequenciação direta/MLPA, foram detetados 42 casos (34,7%) com alterações num dos BRCA’s (excluindo polimorfismos), correspondendo a 42-45 alelos mutados. No entanto, apenas 8,3% dos casos continham mutações comprovadamente patogénicas, representando a mutação fundadora portuguesa 40% das mesmas. Comparativamente a outros estudos na população portuguesa, a prevalência de mutações patogénicas no nosso estudo foi inferior, com uma sobrerepresentação da mutação fundadora, o que poderá ser explicado por diferentes critérios de referenciação e/ou composição das amostras estudadas. O algoritmo BRCAPro® revelou-se útil como instrumento de cálculo de probabilidade de mutação patogénica nos genes BRCA1 e BRCA2, embora não permita substituir o critério médico na de seleção de pacientes para estudo genético destes genes.
Breast cancer is the type most common malignant neoplasm in women worldwide. In most cases arises sporadically, but it is estimated that about 7% have a hereditary origin, related to the genetic inheritance of some pathogenic mutation in susceptibility genes for this cancer. The most frequent cause of hereditary breast/ovarian cancer is an alteration in one of the two BRCA genes, the BRCA1 and BRCA2. Germline mutations in these two genes are responsible for about 50% of cases with hereditary breast and ovarian cancer. Currently, few data is available referring to the mutation profile in the Portuguese population, besides the identification of a founder mutation in the BRCA2 gene. It was intended with this study to characterize, in a sample constituted of patients with suspicion of hereditary breast/cancer, mutations of these two genes, evaluating the different types of mutations found, the prevalence of pathogenic mutations, particularly the Portuguese founder mutation. It was also intended to test the algorithm BRCAPro®, in the aid of recruitment of patients for genetic testing with suspected HBOC. Of the 121 cases studied by DGGE/direct sequencing/MLPA, we detected 42 cases (34,7%) containing alterations in one of the BRCA genes (excluding polymorphisms), corresponding to 42-45 mutated alleles. After analysis, only 8.3% of the cases had deleterious mutations, with the founder Portuguese mutation representing 40% of those. Comparing to other studies in the Portuguese population, the prevalence of pathogenic mutations found in this study was smaller, with an overexpression of the Portuguese founder mutation. That can be explained by the use of different clinical criteria in the recruitment of patients for genetic study and/or differences in the composition of the cohort of cases. The BRCAPro® algorithm as proved useful as a tool for the calculation of mutation probability in the BRCA1 and BRCA2 genes, although it doesn’t allow to substitute the medical criteria in the selection of patients for genetic study in this two genes.
Escobar, Karina Augusto. "Determinação de mutações e polimorfismo nos genes BRCA1 e BRCA2 em pacientes com câncer de mama com indicação para teste genético." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-05092011-152557/.
Full textIntroduction: Mutation in BRCA1 and BRCA2 genes are responsible for more than 50% of hereditarian breast and ovarian cancer cases. Nowadays, we still dont know the Brazilian mutation profile for these genes, except when founder mutations occur in specific ethnic groups. Objetives: Detection of mutation and polymorphisms in BRCA1 and BRCA2 genes in 73 breast cancer patients selected for genetic testing. Casuistic and methods: we have realized direct sequencing of BRCA1 and BRCA2 in 73 patients, whose 63 have had breast cancer and showed at least 10% of risk according to Frank, Evans and BRCAPRO, two patients with ovarian cancer and eight healthy individuals of strong family history of cancer linked to mutations in BRCA1 and BRCA2. Results: We have found 60 mutations in BRCA1: 13 missense mutations (including the deleterious R71G), seven synonymous mutations, one frameshift mutation (the deleterious 5382insC), one nonsense mutation (the deleterious R1751X), one in-frame deletion, one 3UTR mutation and 36 intronic variants. In BRCA2 we have found 57 mutations: 26 missense mutations, one 5UTR mutation, 11 synonymous mutations, 14 intronic variants, two nonsense mutations (the deleterious R2318X and R3128X) and three frameshift mutations (5844del5, 6610insTT and 6633del5). No mutation was detected by MLPA technique. Discussion and final considerations: Nine of 73 studied individuals carry deleterious mutations. Among them, the Ashkenazi founder mutation 5382insC has been found in two unrelated patients and it was previously reported by another research group for its high prevalence on a population from São Paulo. Alterations of unknown clinical significance have been found all over BRCA1 and BRCA2 gene extension and are countless. Some of them are shown only in one patient, leading us to think that maybe one or a few might have a pathogenic effect, like 6610insTT, which leads to a BRCA2 incomplete protein and was shown in 3 generations of a family. MLPA technique have not detected large genomic rearrangements in both genes, showing that this kind of mutation is not frequent on our cohort and maybe this genetic alteration characterizes less miscigenated populations. So, we emphasize the importance of enlarge this study and stimulate future researches, aiming an efficient genetic counseling, decreasing inconclusive cases generated by unknown clinical significance variants, and follow up of affected families
Elliott, Diana. "The impact of genetic counselling for familial breast cancer on women's psychological distress, risk perception and understanding of BRCA testing." University of Western Australia. School of Population Health, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0190.
Full textSantana, dos santos Elizabeth. "Contribution of the Missense and Non-Coding BRCA1/2 Variants for the Hereditary Predisposition and Response to Treatment of Breast and Ovarian Cancers Assessment of the Functional Impact of Germline BRCA1/2 Variants Located in Non- Coding Regions in Families with Breast and/or Ovarian Cancer Predisposition Non-Coding Variants in BRCA1 and BRCA2 Genes: Potential Impact on Breast and Ovarian Cancer Predisposition." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASS027.
Full textOvarian and breast cancers are currently defined by the main pathways involved in the tumorigenesis. In hereditary breast/ovarian cancers (HBOC), tumors with BRCA1/2 pathogenic variants (PV) present an impairment of DNA repair by homologous recombination (HR). For many years, BRCA1/2 PV were only searched on germline DNA. Currently, this information is also searched at tumor level to personalize treatment. Even so, the reason of the inactivation of this pathway remains uncertain for most cases, even in the presence of HR deficient signature.Gathered evidence indicates that protein inactivating PV may not be the only mechanism of HR dysfunction. In this context, the main objective of this thesis is to identify alternative mechanisms of HR inactivation to improve both: genetic counseling and therapeutic response. For this purpose, we have attempted to contribute to non-coding and missense (other than premature stop codon) BRCA1/2 variant classification and searched for new biomarkers of therapeutic response to DNA damage agents in other HR genes.We identified germline variants in key transcriptional regulatory elements of BRCA1 and BRCA2, and demonstrated that part of them were functionally active and had additional arguments suggesting pathogenicity. We also explored molecular features of breast and ovarian tumors from BRCA1 variant carriers and observed a predominance of loss of the wild-type allele. Conforming to this evidence, we propose to incorporate LOH information, into the multifactorial model for BRCA1 variant classification. Finally, besides the enrichment of BRCA1/2 germline and somatic PV, we described alternative mechanisms of HR inactivation in a OC population presenting optimal response to platinum-based chemotherapy, including BRCA1 promoter hypermethylation and also mutations in other genes of HR pathway
Rapakko, K. (Katrin). "Hereditary predisposition to breast cancer—evaluation of candidate genes." Doctoral thesis, University of Oulu, 2007. http://urn.fi/urn:isbn:9789514284502.
Full textHuusko, P. (Pia). "Predisposing genes in hereditary breast and ovarian cancer." Doctoral thesis, University of Oulu, 1999. http://urn.fi/urn:isbn:9514254422.
Full textRAMALHO, Eduardo Augusto Vasconcelos de Freitas. "Avaliação de alterações nos genes p53, BRCA1 em Carcinoma Ductal Invasivo de Mama (CDI)." Universidade Federal de Pernambuco, 2012. https://repositorio.ufpe.br/handle/123456789/10853.
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CAPES
Sabe-se que os genes p53, BRCA1 e BRCA2 apresentam a característica em comum de serem considerados supressores tumorais. Eventos genéticos e epigenéticos são frequentes ao longo de todo o genoma humano. Mutações somáticas são passíveis de ocorrer nas regiões codificantes de genes específicos, alterando sua sequência e gerando proteínas mutantes, as quais resultam numa alteração de sua capacidade funcional ou até mesmo a perda dela. Este trabalho objetivou avaliar alterações epigenéticas nas regiões promotoras dos genes BRCA1 e BRCA2 através da técnica de PCR para Metilação Específica (MSP) e correlacionar mutações pontuais nos exons 4 e 7 do gene p53 como fator de risco para o carcinoma ductal invasivo (CDI) de mama na população feminina do Recife atendida no Hospital das Clínicas (HCUFPE). Cinquenta biópsias de mama diagnosticadas com CDI fixadas em formalina e embebidas em parafina foram obtidas do Setor de Anatomia Patológica do HC-PE e cinco amostras de tecido mamário de mulheres submetidas à mastectomia estética foram usadas como controle normal. O DNA das amostras foram extraídos e, então, amplificados por MSP. Para avaliação do perfil mutacional utilizou-se a técnica de PCR-RFLP (Restriction Fragment Length Polymorphism) com as enzimas BstUI e HaeIII para verificação dos polimorfismos nos exons 4 e 7, respectivamente. A frequência no padrão de metilação para o gene BRCA2 foi de 46,9% enquanto a frequência de mutações pontuais nos códons 72 (exon 4) e 249 (exon 7) do gene p53 foram de 91,8% e 8,1%, respectivamente. Para o BRCA1 os resultados obtidos foram inconsistentes quanto ao seu padrão de metilação. Os resultados mostraram que o polimorfismo do códon 72 apresentou-se estatisticamente significante para metástase podendo ser utilizado como um potencial biomarcador auxiliar no diagnóstico de carcinoma ductal invasivo de mama humana.
Margolin, Sara. "Family history and breast cancer susceptibility : clinical and molecular studies /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-868-1/.
Full textMaguire, Paula. "Investigation of the genetic basis of familial non-BRCA1/2 breast cancer /." Stockholm, 2005. http://diss.kib.ki.se/2006/91-7140-602-6/.
Full textAlwahiby, Suliman Abdullah M. "Molecular cytogenetic analysis of telomeres in cells with mutant BRCA1 and BRCA2 genes." Thesis, Brunel University, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425381.
Full textLiu, Wei. "Genetic analysis of the BRCA1 and BRCA2 genes in breast cancer of Hong Kong Chinese." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/HKUTO/record/B39558848.
Full textVallée, Maxime. "Design of an internet tool to assess variants of uncertain clinical significance in high-risk breast cancer genes BRCA1 and BRCA2." Thesis, Lyon 1, 2012. http://www.theses.fr/2012LYO10193.
Full textGermline mutations in major breast cancer susceptibility genes BRCA1 and BRCA2 are responsible for the disease for high-risk patients (patients with early onset and familial history of breast cancer). Around 15% of screened women for BRCA1 and BRCA2 mutations carry one clearly pathogenic mutation in one of those two genes. However, variants of uncertain clinical significance (VUS) are detected in 5% to 15% of tested patients. To assess clinical significance of VUS, the Breast cancer Information Core (BIC) has developed a Bayesian integrated model, based on observational data. Align-GVGD, an algorithm evaluating damage of missense substitutions based on the evolutionary history of the protein, is providing the prior probability of the model. However, whenever a silent substitution arise, it is firstly treated as neutral by the in silico assessment. Indeed, a mutation at the mRNA level can disrupt the splicing machinery by two main means: damaging wild-type splice sites, or creating exonic de novo splice sites. Our first goal is to be a central repository of already published variants, to re-analyze them using the unified integrated evaluation model. We would like to extract the most variants from the original published status of VUS to a more informative status, with associated clinical recommendations. Then we would like to extend the model to be able to evaluate more variants more precisely by adding the splicing damages assessment in the integrated evaluation. In the end, we will be able to provide these informations freely on Internet, via a widely use web interface, a Leiden Open Variation Database (LOVD)
Goveia, Rebeca Mota. "Análise de deleção/ duplicação nos genes BRCA1 e BRCA2 em pacientes de Goiás-Brasil com suspeita da síndrome do câncer de mama e ovário hereditário." Universidade Federal de Goiás, 2018. http://repositorio.bc.ufg.br/tede/handle/tede/8723.
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Introduction: Breast cancer is the second most common cancer in the world, and the most common among women, only 5% to 10% are hereditary and half of them are caused by hereditary breast and ovarian cancer (HBOC) , caused by variations in the BRCA1 and BRCA2 genes. Objectives: The present study aimed to identify the prevalence of deletions and duplications in BRCA1 and BRCA2 genes in breast cancer patients in Goiás, Brazil. Materials and methods: We evaluated 46 breast cancer patients who met National Comprehensive Cancer Network (NCCN) criteria for HBOC syndrome screening. A 4 ml blood sample was collected for DNA extraction using commercial kit and the MLPA (Multiplex Ligation Dependent Probe Amplification) technique was performed using the SALSA MLPA P002 BRCA1 and SALSA MLPA P045 BRCA2 / CHECK2 kits. Results and discussion: The majority of the patients were female (97.83%) and the mean age of the patients was 37.52 years. In this group, 43.47% of the patients were younger than 35 years at the time of diagnosis and 35% of them were diagnosed with triple negative tumors. The most common molecular subtype was luminal A (46.2%) followed by triple negative tumors (28.20%). No patient was found with rearrangements in BRCA1. In the BRCA2 gene, one patient (2.12%) presented a false positive result for the heterozygous deletion of exon 27, which may have been caused by the presence of a small change in the probe binding region. Conclusion: This was the first study performed to analyze large deletions and duplications in patients from the central-western region of Brazil. We can conclude that the frequency of large deletions and duplications in the BRCA1 and BRCA2 genes in the Goian population is low.
Introdução: O câncer de mama é o segundo tipo de câncer mais freqüente no mundo, e o mais comum entre as mulheres, apenas 5% a 10% são hereditários e metade deles são causados pela síndrome do câncer de mama e ovário hereditário (HBOC), causada por variações nos genes BRCA1 e BRCA2. Objetivos: O presente estudo teve como objetivo identificar a prevalência de deleções e duplicações nos genes BRCA1 e BRCA2 em pacientes com câncer de mama no estado de Goiás, Brasil. Materiais e métodos: Avaliamos 46 pacientes com câncer de mama que atenderam aos critérios do National Comprehensive Cancer Network (NCCN) para pesquisa da síndrome HBOC. Foi coletada uma amostra de sangue de 4 ml para extração de DNA usando kit comercial e a técnica MLPA (Multiplex Ligation Dependent Probe Amplification) foi realizada usando os kits SALSA MLPA P002 BRCA1 e SALSA MLPA P045 BRCA2 / CHECK2. Resultados e discussão: A maioria dos pacientes era do sexo feminino (97.83%) e a idade média dos pacientes era de 37,52 anos. Neste grupo 43.47% dos pacientes possuíam idade inferior a 35 anos no momento do diagnóstico sendo que 35% destes foram diagnosticados com tumores triplo negativo. O subtipo molecular mais comum foi o luminal A (46.2%) seguido de tumores triplo negativos (28.20%). Nenhum paciente foi encontrado com rearranjos no gene BRCA1. No gene BRCA2, um paciente (2,12%) apresentou um resultado falso positivo para a deleção em heterozigoze do éxon 27, fato que pode ter sido ocasionado pela presença de uma pequena alteração na região de ligação da sonda. Conclusão: Este foi o primeiro estudo realizado para análise de grandes deleções e duplicações em pacientes da região centro-oeste do Brasil. Podemos concluir que a frequência de grandes deleções e duplicações nos genes BRCA1 e BRCA2 na população goiana é baixa.
Liu, Wei, and 劉蔚. "Genetic analysis of the BRCA1 and BRCA2 genes in breast cancer of HongKong Chinese." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39558848.
Full textDiz, Maria Del Pilar Estevez. "Impacto do encaminhamento para ambulatório de câncer hereditário na qualidade de vida de pacientes portadores de câncer de mama." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-20082007-161259/.
Full textHere we evaluated the impact of breast cancer hereditary cancer risk evaluation on the quality of life in a population of breast cancer patients, as measured by the EORTC questionnaires QLQ-C30 and QLQ-BR23. Of the 282 invited patients, 272 agree to participate and answered QLQ before and after the risk determination by Frank, Evans and BRCAPRO methods. High risk was defined as at least 10%. Overall 198 pts completed the study. In the 180 evaluable patients, median age was 53 (+11,5) years old and time since diagnosis was less than 36 months in 89. We did not detected significant differences in quality of life parameters after risk determination, except for negative body image and mastectomy/conservative surgery (p<0.001) There were 45 patients classified as high risk by Frank, 35 by the BRCAPRO and 21 by Evans, agreement being reached in 12. We conclude that pts wish to know about their hereditary breast cancer risk, and this do not cause necessarily more stress. Apart from that, there is a need for local methods of risk calculation.
Becker, Alexandra Angela [Verfasser]. "Funktionelle Analyse unklassifizierter Varianten der Gene BRCA1 und BRCA2 / Alexandra Angela Becker." Köln : Deutsche Zentralbibliothek für Medizin, 2013. http://d-nb.info/1045459046/34.
Full textMARGARESE, Naomi. "Genetic analysis of BRCA1 and BRCA2 genes in Sicilian high risk families and functional characterization of BRCA1 variants of uncertain significance (VUS)." Doctoral thesis, Università degli Studi di Palermo, 2014. http://hdl.handle.net/10447/90823.
Full textOh, Yeum Mok, and Yeum Mok Oh. "BRCA1 and BRCA2 Gene Mutations in Colorectal Cancer: A Systematic Review and Meta-Analysis." Thesis, The University of Arizona, 2017. http://hdl.handle.net/10150/625685.
Full textLitman, Rachel. "Characterization of the BACH1 Helicase in the DNA Damage Response Pathway: a Dissertation." eScholarship@UMMS, 2007. https://escholarship.umassmed.edu/gsbs_diss/329.
Full textNovak, David. "A multifaceted approach to elucidating the role of BRCA1- and BRCA2- related genes in hereditary breast cancer." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86576.
Full textA combination of genotyping 96 BRCA1/2 negative, high risk breast cancer patients and segregation analysis was utilized in the determination of whether or not RAP80 and Abraxas are breast cancer susceptibility genes. The contribution of CHEK2 associated breast cancer amongst the French Canadian population was determined through the genotyping 25 BRCA1/2 negative, high risk breast cancer and a cohort of 25 controls. Finally, the biological significance of four PALB2 susceptibility alleles was investigated through the use of the cellular cytotoxicity assay WST-1, telomere specific Q-FISH, centromere specific FISH and spectral karyotyping.
The results presented herein suggest that both RAP80 and Abraxas are not high to moderately penetrant breast cancer susceptibility genes. Further, our results suggest that alleles other than the CHEK2 1100delC are unlikely to significantly contribute to the hereditary breast cancer risk in the French Canadian population. Lastly, the results obtained throughout our analysis of PALB2 heterozygous cell lines may be suggestive of a possible chromosomal instability phenotype predisposing carriers to additional tumourgenic mechanisms.
5-10% des cas de cancer héréditaire du sein sont causés par des mutations germinales dans des gènes des susceptibilité bien caractérisés et à l'effet dominant tel les gènes BRCA1 et BRCA2. Cependant, plus de 50% de la prédisposition génétique au cancer du sein héréditaire demeure inexpliquée. Dans cette thèse, nous présentons une approche à trois volets ayant pour but d'étudier les cas de cancer héréditaire du sein associés avec des gènes interagissant avec BRCA1 et BRCA2. D'abord, nous analysons la contribution potentielle de deux gènes peu caractérisés qui sont partenaires de BRCA1 : RAP80 et Abraxas. Nous étudions ensuite le risque associé avec la présence d'allèles nouveaux ou connus du gène CHEK2 jamais encore caractérisés dans la population canadienne française. Enfin, nous examinons les mécanismes cellulaires et moléculaires responsables de l'augmentation du risque de cancer du sein conférée par des allèles à risque du gène PALB2.
Nous avons utilisé une combinaison de génotypage chez 96 patients souffrant du cancer du sein mais étant non porteurs de mutations dans BRCA1/2 et d'analyse de ségrégation des mutations et des phénotypes dans leurs familles afin de déterminer si RAP80 et Abraxas sont ou non des gènes de prédisposition au cancer héréditaire du sein. La contribution au risque de cancer du sein du gène CHEK2 fût déterminée grâce au génotypage de 25 cas à haut risque, non porteurs de mutations chez BRCA1/2, et de 25 contrôles sans cancer. Finalement, nous avons étudié 4 allèles nonsense du gène PALB2 à l'aide du test de toxicité cellulaire WST-1 ainsi qu'en utilisant l'analyse Q-FISH spécifique aux télomères, l'analyse FISH spécifique aux centromères et finalement par caryotype spectral (SKY).
Les résultats présentés dans cet ouvrage suggèrent que RAP80 et Abraxas ne sont pas des gènes de susceptibilité au cancer du sein à pénétrance moyenne ou élevée. De plus, il est peu probable que des allèles du gène CHEK2 autres que l'allèle connu 1100delC contribuent de façon significative au risque de cancer du sein héréditaire dans la population canadienne française. Par contre, les résultats de notre analyse du gène PALB2 dans les lignées cellulaires hétérozygotes pour un allèle nonsense suggèrent la possibilité que la présence de ces allèles crée de l'instabilité chromosomique chez les porteurs de mutations qui puissent prédisposer à la progression tumorale.
Santos, Catarina Gomes Rodrigues. "Avaliação da patogenicidade de mutações germinativas de significado desconhecido nos genes BRCA1 e BRCA2 em famílias portuguesas." Master's thesis, Instituto de Ciências Biomédicas Abel Salazar, 2008. http://hdl.handle.net/10216/9163.
Full textSantos, Catarina Gomes Rodrigues. "Avaliação da patogenicidade de mutações germinativas de significado desconhecido nos genes BRCA1 e BRCA2 em famílias portuguesas." Dissertação, Instituto de Ciências Biomédicas Abel Salazar, 2008. http://hdl.handle.net/10216/9163.
Full textRamos, Marcelo Cristiano de Azevedo. "Análise de custo-efetividade de programa para diagnóstico de mutação germinativa em genes BRCA1/2 e de estratégias preventivas para pacientes com câncer de ovário e seus familiares de primeiro grau." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-09052018-082903/.
Full textINTRODUCTION: Several professional societies recommend performing genetic tests for women who have developed ovarian cancer in order to identify BRCA1/2 germline-mutation carriers and offer risk-reducing therapy. OBJECTIVE: The objective of this study was to perform a cost-effectiveness analysis of a BRCA1/2 germline mutation diagnosis program and preventive strategies for patients diagnosed with ovarian cancer and their first degree relatives. METHODS: The study performed a cost-effectiveness analysis through the development of a Markov decision model and the perspective of the Unified Health System. The compared strategies reflected the adoption of genetic testing and preventive strategies for patients and their relatives or the usual follow-up. The incremental cost-effectiveness ratio was expressed in terms of cost per avoided case of cancer. Sensitivity analysis was performed in a univariate and deterministic manner. RESULTS: There has been an increase in effectiveness and in costs with genetic testing and the adoption of prophylactic measures for patients and their relatives. The incremental cost-effectiveness ratio was calculated at R$ 14,224.40 and R$ 908.58, respectively, for avoided cases in patients with prior diagnosis of ovarian cancer and their first-degree relatives. These values were considered lower than the cost-effectiveness threshold selected in the study (from R$ 7,543.50 to R$ 23,786.70). DISCUSSION: The analyzed program can be considered as a cost-effective strategy for the national reality, especially in relation to the first-degree relatives of patients with ovarian cancer. Other publications have shown similar conclusions for the subject in several countries. CONCLUSION: A possible development of this work could be represented by a budget impact analysis of the incorporation of the program as health policy in Brazil
Palfner, Sonja. "Gen-Passagen molekularbiologische und medizinische Praktiken im Umgang mit Brustkrebs-Genen ; Wissen - Technologie - Diagnostik." Bielefeld Transcript, 2008. http://d-nb.info/994330804/04.
Full textGalvão, Violeta Regnier. "Biomarcadores na anafilaxia a platinas." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-27032018-133113/.
Full textINTRODUCTION: Cancer is the leading cause of death in the age group of 45 to 84 years, and one of the main public health issues in developing nations. Hypersensitivity reactions to chemotherapeutic agents have been increasing, sometimes hindering the use of first-line therapies in the treatment of primary or relapsed tumors. Rapid drug desensitization (RDD) is an alternative approach, through which a patient becomes tolerant to the medication that once triggered a potentially lethal hypersensitivity reaction. Platinum-based compounds are examples of drugs that can be readministered through the desensitization procedure, but currently there are no known biomarkers that could help predict reactions during RDD. OBJECTIVES: The main goal of our study was to assess the basophil activation test (BAT) as a biomarker of breakthrough reactions occurred during RDD in patients allergic to platinum-based agents. As a secondary goal, we evaluated the prevalence and impact of the BRCA 1/2 mutation in carboplatin-allergic patients undergoing RDD. METHODS: We standardized the BAT by evaluating CD63 and CD203c expressions on the basophils of patients with immediate hypersensitivity reactions to platinum-based agents undergoing RDD. We analyzed BATs of 15 patients with malignant neoplasms who had undergone 27 RDD procedures due to anaphylaxis to platinum-based agents, and of 12 control subjects (Group 1: six patients tolerant to platinum-based agents, and Group 2: six healthy volunteers who had never been exposed to platinum-based agents). BAT results were compared among the three groups. We correlated BAT results with the occurrence of breakthrough reactions during RDD and with serum tryptase levels. To conduct the analysis of the BRCA 1/2 mutation prevalence and its impact on RDD, a retrospective review of 138 medical records of patients with gynecological malignancies who underwent RDD to carboplatin was performed. RESULTS: BAT was positive in 11/15 allergic patients (73.3%), with increased expression of CD203c and CD63 in 11 (73.3%) and 6 (40%) patients, respectively. All control subjects presented negative BATs. A higher CD63 expression was observed in patients with severe initial reactions. BAT was positive in 92.3% of the breakthrough reactions occurred during RDD (n=12/13), and in all reactions with concomitant increased tryptase levels (n=5). Regarding the BRCA1/2 mutation, its prevalence was 34% in patients allergic to platinum-based agents (n=47/138), and 51% of the mutation carriers had breakthrough reactions during RDD. CONCLUSIONS: A positive BAT, with an increased expression of CD63 and/or CD203c, identified patients allergic to platinum-based agents with a specificity of 100% and a sensitivity of 73.3%. The BAT and the BRCA 1/2 mutation helped identify patients at risk of breakthrough reactions during RDD. The use of predictive biomarkers of breakthrough reactions during RDD to platinum-based agents might enhance RDD safety and help maintain a patient`s first-line treatment
Gedminaitė, Jurgita. "Krūties vėžiu sergančių moterų BRCA1, BRCA2, CHEK2 ir NBS1 genų mutacijų tyrimas ir jų ryšio su kitais prognoziniais veiksniais paieška." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2013. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2013~D_20130919_143947-94587.
Full textApproximately 5–10% of all breast cancer cases are considered to be hereditary. BRCA1 and BRCA2 genes are the most important breast cancer predisposing genes. Other genes significantly linked with an increased risk of breast tumors are CHEK2 and NBS1 gene. In this scientific work were studied the most prevalent in European region mutations of these genes. The rate of BRCA1 and CHEK2 gene mutations in young women with breast cancer was evaluated and the relationships between these mutations and patient's age, clinical and morphological tumor features are examined. The prognostic value of family history was analyzed when forecasting hereditary BRCA1 and CHEK2 gene mutations. For the first time in Lithuania the CHEK2, NBS1 genes tests were applied and the evaluation of which CHEK2 gene mutations are most prevalent was obtained. Although NBS1 gene mutations were not found, but applied test technique will be used in future research. There was created a prognostic model for determination of BRCA1 and CHEK2 gene mutations. In today's clinical practice similar models are used to assess the likelihood of the BRCA1/2 mutation. Their applicability and specificity in different ethnic groups may vary. Applying the studied data there was created a model adapted to our region. Testing patients, there were considered not only family medical history and personal characteristics, but also the clinical and molecular features of tumors. The criteria have been found which will help in selecting... [to full text]
Marafie, Makia. "Investigations of BRCA1 or BRCA2 gene changes in women affected by early onset breast or ovarian cancer." Thesis, University of Nottingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311839.
Full textPadilla, Sirera Natàlia. "Novel approaches for in silico identification of pathogenic variants in BRCA1 and BRCA2 hereditary breast and ovarian cancer predisposition genes." Doctoral thesis, Universitat Autònoma de Barcelona, 2020. http://hdl.handle.net/10803/670705.
Full textVariantes germinales en las proteínas BRCA1 y BRCA2 pueden alterar la función protectora de estas en el ADN, incrementando el riesgo de desarrollar cáncer de mama y ovario hereditario (HBOC). Identificación de aquellos individuos portadores de variantes patogénicas permite canalizarlos hacia programas específicos de prevención y vigilancia, aumentando sus tasas de supervivencia. Para ello, en primer lugar, es necesario identificar cuáles de las variantes son patogénicas. Desafortunadamente, no siempre hay suficiente información para llegar a una conclusión. En esta situación, los predictores de patogenicidad diseñados para estimar computacionalmente el daño causado por las variantes pueden proporcionar una valiosa información. En este trabajo presentamos una nueva familia de predictores de patogenicidad para BRCA1 y BRCA2. Estos predictores difieren en su objetivo: uno está entrenado para estimar el impacto molecular de las variantes en la función HDR de BRCA1 y BRCA2, y el otro está entrenado para estimar la significancia clínica de una variante, es decir, si su clasificación es patogénica o neutra. Sus rendimientos han sido probados y son comparables a los de los métodos ampliamente utilizados en el campo. Además, presentamos los predictores al desafío ENIGMA de la 5ª Evaluación Crítica de la Interpretación del Genoma (CAGI), encontrando que nuestros métodos, especialmente aquellos que estiman el impacto funcional de las variantes, se clasifican en las primeras posiciones en comparación con las otras herramientas. Para difundir esta familia de predictores a la comunidad científica, hemos construido el sitio web BRASS (https://www.biotoclin.org/BRASS), donde los usuarios pueden analizar sus variantes de BRCA1 y BRCA2 con cambio de sentido. Los usuarios más avanzados también pueden interpretar las predicciones utilizando una métrica de confiabilidad y varios gráficos que contextualizan su puntuación a la de un conjunto de variantes seleccionadas manualmente. De forma independiente, aplicamos nuestro conocimiento sobre los predictores de patogenicidad en un gran proyecto internacional para caracterizar un nuevo trastorno neurológico pediátrico causado por variantes patogénicas en la histona H3.3. Combinamos el uso de predictores patogénicos estándar con evidencia de análisis estructurales y cálculos biofísicos para proporcionar una visión mecanicista del impacto de las variantes causales.
Germline variants in BRCA1 and BRCA2 can disrupt the DNA protective role of these proteins resulting in an increased risk of developing hereditary breast and ovarian cancer (HBOC). Identification of those individuals carrying pathogenic variants will allow channeling them into specific programs of prevention and surveillance, incrementing their survival rates. For this purpose, first, it is necessary to identify which of the variants are pathogenic. Unfortunately, there is not always enough information to reach a conclusion. In this situation, pathogenicity predictors designed to computationally estimate the damage caused by variants, can provide valuable information. Here, we present a novel family of pathogenicity predictors for BRCA1 and BRCA2. These predictors differ in their objective: one is trained to estimate the molecular impact of variants on the HDR function of BRCA1 and BRCA2, and the other is trained to estimate the clinical significance of a variant, that is, whether it should be classified as pathogenic or neutral. Their performances have been tested and are comparable to those of widely used predictors in the field. Additionally, we presented them to the ENIGMA challenge from the 5th Critical Assessment of Genome Interpretation (CAGI), finding that our predictors, especially those estimating the functional impact of variants, ranked in the top positions compared to other tools. In order to disseminate this family of predictors to the scientific community, we have built the BRASS website (https://www.biotoclin.org/BRASS), where users can analyze their missense BRCA1 and BRCA2 variants. More advanced users can also interpret the predictions using a reliability metric and several plots contextualizing the score to that of a set of manually curated variants. Independently, we applied our knowledge about pathogenicity predictors in a large international effort to characterize a novel pediatric neurologic disorder caused by pathogenic variants in histone H3.3. We combined the use of standard pathogenic predictors with evidence from structural analyses and biophysical computations to provide a mechanistic view of the impact of the causative variants.
Reilly, Drew D. "The Narratives of Young Women with BRCA 1/2 Gene Mutation: A Qualitative Analysis." ScholarWorks@UNO, 2014. http://scholarworks.uno.edu/td/1910.
Full textDufloth, Rozany Mucha. "Carcinoma de mama hereditario em mulheres brasileiras : mutações dos genes BRCA1 e BRCA2, polimorfismos dos genes de reparo do DNA e caracterização imunoistoquimica pela tecnica de Tissue Microarray." [s.n.], 2004. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313286.
Full textTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-04T01:21:30Z (GMT). No. of bitstreams: 1 Dufloth_RozanyMucha_D.pdf: 623963 bytes, checksum: 756d732465da74e705449411420fb717 (MD5) Previous issue date: 2004
Resumo: OBJETIVOS: Identificar mutações nos genes BRCA1 e BRCA2 em uma população brasileira com câncer de mama hereditário; analisar a freqüência de polimorfismos nos genes XRCC1, XPD, XRCC3 e RAD51 em um grupo de pacientes brasileiras e sua associação com a susceptibilidade ao câncer de mama; analisar expressão das proteínas p63, CK5 e P-caderina em cânceres de mama familiar e esporádico. MÉTODOS: Este estudo teve componentes do tipo transversal e do tipo caso-controle. Foram constituídos quatro grupos: pacientes com câncer hereditário de mama; pacientes com câncer de mama esporádico; mulheres sem câncer de mama e com história familiar positiva de câncer de mama e/ou ovário; mulheres sem câncer de mama e sem história familiar de câncer de mama e/ou ovário. Foram coletados 10ml de sangue periférico para a realização de técnicas moleculares, nomeadamente Single Strand Conformation Polymorphism (SSCP) e Seqüenciação Direta. Espécimes de câncer de mama, conservados em blocos de parafina, foram selecionados no Laboratório de Patologia do Hospital das Clínicas/Unicamp, Brasil e no Laboratório de Patologia do Hospital São João/Universidade do Porto, Portugal, totalizando 168 casos. Dos blocos doadores foram extraídos cilindros de 2mm de diâmetro e depositados nos blocos de parafina receptores, usando Tissue Microarrayer (Beecher Instrumensts, Silver Spring, Maryland). Nestes cortes foi feita a pesquisa dos marcadores de diferenciação do fenótipo basal/mioepitelial. RESULTADOS: Foram identificadas quatro mutações (13%), sendo uma mutação no gene BRCA1 e três no gene BRCA2. No BRCA1 foi encontrada uma mutação do tipo frameshift. Duas mutações do BRCA2 são tipo nonsense e a outra do tipo unclassified variant. Não houve associação estatisticamente significante entre os alelos e genótipos dos polimorfismos dos genes de reparo do DNA, XRCC1, XPD, XRCC3 e RAD51. O câncer de mama familiar mostrou diferenças estatisticamente significantes do fenótipo imunoistoquímico dos marcadores de células basais/mioepiteliais (P-caderina, p63 and CK5), em relação aos cânceres esporádicos. CONCLUSÃO: Foram identificadas uma mutação no gene BRCA1 e três mutações no gene BRCA2 em mulheres com câncer de mama e história familiar de câncer de mama, o que correspondeu a uma freqüência de 13% (4/31). Não foi observada associação da susceptibilidade ao câncer de mama com os polimorfismos dos genes XRCC1, XPD, XRCC3 e RAD51 em um grupo de pacientes brasileiras. Os marcadores p63, CK5 e P-caderina foram mais freqüentemente expressos no câncer de mama familiar. A melhor caracterização do câncer familiar como entidade biológica distinta do câncer esporádico pode ser uma ferramenta útil para selecionar mulheres que deveriam submeter-se ao rastreamento de mutações nos genes BRCA1 e BRCA2
Abstract: OBJECTIVE: To identify mutations in BRCA1 and BRCA2 genes in a Brazilian population of women with hereditary breast cancer; to analyze the frequency of polymorphism in genes XRCC1, XPD, XRCC3 e RAD51 in a group of Brazilian patients and its association with breast cancer susceptibility; to analyze the expression of p63, CK5 and P-cadherin proteins in familial and sporadic breast cancers. METHODS: This study was in part transversal and in part crosssectional. The population evaluated in this study comprised four groups of women: patients with sporadic and familial breast cancers, women without breast cancer but with family history, women without breast cancer and without family history. The last group was the control group of this study. From each subject, 10ml of peripheral blood were collected to perform molecular analysis, namely Single Strand Conformation Polymorphism (SSCP) and Direct Sequencing. Paraffin blocks from breast cancer specimens were selected from the Pathology Laboratories from the Hospital das Clínicas/UNICAMP, Brazil and Hospital São João/Universidade do Porto, Portugal, totalising 168 cases. Cylinders with 2mm diameter were extracted from the donnor blocks using the Tissue Microarrayer technique (Beecher Instruments, Silver Spring, Maryland), and were sampled together to construct the receptor paraffin blocks. The analysis of mioepithelial differentiation/histogenesis was performed in these sections. Results analysis was carried out through the Chi-square test. RESULTS: Four mutations were identified: one in BRCA1 and three in BRCA2. A frameshift BRCA1 mutation, two nonsense BRCA2 and one unclassified variant BRCA2 mutation were identified. No statistically significant association between the alleles and genotypes DNA, XRCC1, XPD, XRCC3 and RAD51 polymorphism. Familial breast cancer was statistically different from sporadic cancer in regards of immunohistochemical phenotypes for basal/mioepithelial cell markers (Pcadherin, p63 and CK5). CONCLUSIONS: Thirteen percent of women with breast cancer and family history of breast cancer had at least one BRCA1 gene mutation and three BRCA2 gene mutations. We do not observe any statistical significance difference in the frequency of alleles and genotype of the genes XRCC1, XRCC3, XPD e RAD51 in the group of patients studied. The markers, CK5 e P-cadherin was more frequently in familial breast cancers. The characterization of familial breast cancer as a biological entity distinct from sporadic cancer might be a useful tool to select women that should be screened to BRCA1 and BRCA2 genes mutation triaging
Doutorado
Ciencias Biomedicas
Doutor em Tocoginecologia
Larochelle, Chantal. "Interactions physiques et fonctionnelles entre la region C-terminale de la protéine BRCA1 et la kinase CDK7." Sherbrooke : Université de Sherbrooke, 2004.
Find full textGonzalez, Rachel Marie. "Reduced BRCA1 expression in breast and ovarian tumorigenesis /." Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/6334.
Full textKotian, Shweta. "Identification of Novel Genes in BRCA1-Regulated Pathways." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1366341897.
Full textJansson, Sandra, and Lisa Candell. "Ett liv i förändring - att bära på mutation i BRCA 1- eller BRCA 2-genen: en skildring av kvinnors upplevelser : En litteraturöversikt." Thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-396781.
Full textBackground: Mutation in the BRCA genes involves a significantly increased risk of developing breast- and ovarian cancer. Knowledge about carrying this gene mutation lead to stress and resulted in psychosocial changes. Nurses needs insight into how this situation affects the individual in order to satisfy the care needs with a person-centered approach. Purpose: The aim of the study was to investigate and depict women’s experience of carrying a mutation in the BRCA 1 or BRCA 2 gene. Method: General literature review with descriptive design. Results was based on ten qualitative original research articles from the databases PubMed and Cinahl. Results: The experience varied woman to women, and emotional patterns were identified between individuals in similar life situations. Many expressed an initial feeling of shock, and uncertainty about the perceived health. They described a need for information, and experienced a lack of knowledge among the caregivers, which resulted in fear of being misled. The study group described feelings of fear and worry for a future cancer diagnosis and how that would affect their families and themselves. They also described that it forced them into a decision making process regarding risk reducing surgery and family planning. Conclusion: These women experienced great levels of worry, anxiety, fear and uncertainty regarding the future. They experienced a need for information that was not satisfied, and also a great need for support. Caregivers need more knowledge about how awareness of gene mutation in BRCA 1 or BRCA 2 can affect the patient. Strategies need to be designed to meet women´s need of information and support. This in order to promote health and ease suffering.
Puget, 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.
Full textPayne, Shannon Renée. "Analysis of BRCA1 genomic structure : novel germline mutations and somatic alterations in breast cancer /." Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/10295.
Full textYassaee, Vahid Reza. "Towards a general strategy for breast cancer : investigation of germline mutations of BRCA1 and BRCA2 genes in Iranian women with early-onset breast cancer." Thesis, University of Sheffield, 2002. http://etheses.whiterose.ac.uk/5987/.
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