UNIVERSIDAD DE BUENOS AIRES DEPARTAMENTO DE FARMACIA Y...

Breast cancer (BC) is a multifactorial disease that results from a complex combination of genetic and environmental factors. The family history of Hereditary Breast and Ovarian Cancer (HBOC) is the main risk factor for this condition. In the polygenic model of susceptibility to BC, the prevalence of...

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Autor principal: Ozkul, María del Carmen
Otros Autores: Cerretini, Roxana Inés
Formato: Tesis de maestría acceptedVersion
Lenguaje:Español
Publicado: Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica 2017
Materias:
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_2068
https://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_2068.dir/2068.PDF
Aporte de:
id I28-R145-HWA_2068
record_format dspace
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
language Español
orig_language_str_mv spa
topic Cáncer de mama
Cáncer de mama/ovario hereditario
TP53
Variantes genéticas patogénicas
Línea germinal
Breast cancer
Hereditary breast / ovarian cancer
TP53
Pathogenic genetic variants
Germ line
Ciencias de la vida
spellingShingle Cáncer de mama
Cáncer de mama/ovario hereditario
TP53
Variantes genéticas patogénicas
Línea germinal
Breast cancer
Hereditary breast / ovarian cancer
TP53
Pathogenic genetic variants
Germ line
Ciencias de la vida
Ozkul, María del Carmen
UNIVERSIDAD DE BUENOS AIRES DEPARTAMENTO DE FARMACIA Y...
topic_facet Cáncer de mama
Cáncer de mama/ovario hereditario
TP53
Variantes genéticas patogénicas
Línea germinal
Breast cancer
Hereditary breast / ovarian cancer
TP53
Pathogenic genetic variants
Germ line
Ciencias de la vida
description Breast cancer (BC) is a multifactorial disease that results from a complex combination of genetic and environmental factors. The family history of Hereditary Breast and Ovarian Cancer (HBOC) is the main risk factor for this condition. In the polygenic model of susceptibility to BC, the prevalence of germline mutations in the TP53 gene in families with HBOC, not associated with mutation in BRCA1 or BRCA2, is being studied worldwide. In the present work, we aimed to determine the presence of pathogenic genetic variants (GV´s) in the hot spot exons in the germinal line of the TP53 gene in patients with HBOC criteria not associated with mutation in BRCA1/2 or Li Fraumeni Syndrome. For this, 74 subjects with BC and / or OC with / without family history of the disease were studied. Genetic analyzes included Sanger sequencing in exons 5, 6, 7 and 8 of the TP53 gene. In this population were found 4 GV's of which 2 were pathogenic (2/74, 2.7%). After a bioinformatic analysis, these deleterious mutations were associated with aggressive pathogenic characteristics. These results generate knowledge that will allow in the future to identify the distribution and frequency of GV´s as susceptibility or risk factors for the development of HBOC, providing the basis for further studies to determine its distribution throughout the country and contribute knowledge of the epidemiological profile genetic basis. Given the great heterogeneity of cancer worldwide, the identification and registration of locally found cases in each area, allow directing the strategies of management of the pathologies, adapting to the population studied.
author2 Cerretini, Roxana Inés
author_facet Cerretini, Roxana Inés
Ozkul, María del Carmen
format Tesis de maestría
Tesis de maestría
acceptedVersion
author Ozkul, María del Carmen
author_sort Ozkul, María del Carmen
title UNIVERSIDAD DE BUENOS AIRES DEPARTAMENTO DE FARMACIA Y...
title_short UNIVERSIDAD DE BUENOS AIRES DEPARTAMENTO DE FARMACIA Y...
title_full UNIVERSIDAD DE BUENOS AIRES DEPARTAMENTO DE FARMACIA Y...
title_fullStr UNIVERSIDAD DE BUENOS AIRES DEPARTAMENTO DE FARMACIA Y...
title_full_unstemmed UNIVERSIDAD DE BUENOS AIRES DEPARTAMENTO DE FARMACIA Y...
title_sort universidad de buenos aires departamento de farmacia y...
publisher Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica
publishDate 2017
url http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_2068
https://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_2068.dir/2068.PDF
work_keys_str_mv AT ozkulmariadelcarmen universidaddebuenosairesdepartamentodefarmaciay
AT ozkulmariadelcarmen busquedadevariantesgeneticaspatogenicasenlalineagerminaldelgentp53enpacientesconcancerdemamaovariohereditarioenargentina
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spelling I28-R145-HWA_20682024-11-12 UNIVERSIDAD DE BUENOS AIRES DEPARTAMENTO DE FARMACIA Y... Breast cancer (BC) is a multifactorial disease that results from a complex combination of genetic and environmental factors. The family history of Hereditary Breast and Ovarian Cancer (HBOC) is the main risk factor for this condition. In the polygenic model of susceptibility to BC, the prevalence of germline mutations in the TP53 gene in families with HBOC, not associated with mutation in BRCA1 or BRCA2, is being studied worldwide. In the present work, we aimed to determine the presence of pathogenic genetic variants (GV´s) in the hot spot exons in the germinal line of the TP53 gene in patients with HBOC criteria not associated with mutation in BRCA1/2 or Li Fraumeni Syndrome. For this, 74 subjects with BC and / or OC with / without family history of the disease were studied. Genetic analyzes included Sanger sequencing in exons 5, 6, 7 and 8 of the TP53 gene. In this population were found 4 GV's of which 2 were pathogenic (2/74, 2.7%). After a bioinformatic analysis, these deleterious mutations were associated with aggressive pathogenic characteristics. These results generate knowledge that will allow in the future to identify the distribution and frequency of GV´s as susceptibility or risk factors for the development of HBOC, providing the basis for further studies to determine its distribution throughout the country and contribute knowledge of the epidemiological profile genetic basis. Given the great heterogeneity of cancer worldwide, the identification and registration of locally found cases in each area, allow directing the strategies of management of the pathologies, adapting to the population studied. Fil: Ozkul, María del Carmen. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica, Argentina Cerretini, Roxana Inés Ozkul, María del Carmen 2017-11-08 El cáncer de mama (CM) es una enfermedad multifactorial que resulta de una combinación compleja de factores genéticos y medioambientales. La historia familiar de Cáncer de Mama y/u Ovario Hereditario (HBOC), es el principal factor de riesgo para este padecimiento. A nivel mundial, en el modelo poligénico de susceptibilidad al CM, se encuentra en estudio la prevalencia de mutaciones en la línea germinal del gen TP53 en familias con HBOC, no asociado a mutación en BRCA1 o BRCA2. En el presente trabajo buscamos determinar la presencia de variantes genéticas (VG´s) patogénicas en los exones ?hot spot? en la línea germinal del gen TP53 en pacientes con criterio de HBOC no asociados a mutación en BRCA1/2 ni Síndrome de Li Fraumeni (SLF). Para ello se estudiaron 74 sujetos con CM y/o CO, con/sin historia familiar de la enfermedad. Los análisis genéticos incluyeron secuenciación por Sanger en los exones 5, 6, 7 y 8 del gen TP53. En esta población fueron encontradas 4 VG´s de las cuales 2 resultaron patogénicas (2/74, 2.7%). Tras un análisis bioinformático, estas mutaciones deletéreas fueron asociadas con características patogénicas agresivas. Estos resultados generan conocimientos que permitirán a futuro identificar la distribución y frecuencia de las VG´s como factores de susceptibilidad o riesgo para el desarrollo de HBOC, proporcionando las bases para estudios posteriores que permitan determinar su distribución en todo el país y aportar el conocimiento del perfil epidemiológico genético local. Dada la gran heterogeneidad del cáncer a nivel mundial, la identificación y registro de los casos encontrados localmente en cada área, permiten dirigir las estrategias de manejo de las patologías, adecuándose a la población estudiada. application/pdf Fundia, Ariela Rivolta, Carina Cotignola, Javier Cáncer de mama Cáncer de mama/ovario hereditario TP53 Variantes genéticas patogénicas Línea germinal Breast cancer Hereditary breast / ovarian cancer TP53 Pathogenic genetic variants Germ line spa Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencias de la vida Biología Molecular Médica Magíster de la Universidad de Buenos Aires Búsqueda de variantes genéticas patogénicas en la linea germinal del gen TP53 en pacientes con cáncer de mama/ovario hereditario en Argentina info:eu-repo/semantics/masterThesis info:ar-repo/semantics/tesis de maestría info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_2068 https://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_2068.dir/2068.PDF