Identificación de variantes germinales en 63 genes de susceptibilidad al cáncer en mujeres colombianas con cáncer de mama no seleccionado

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dc.contributor.advisorSierra Díaz, Diana Carolina
dc.contributor.advisorOspina Lagos, Sandra Yaneth
dc.contributor.authorSilva Igua, Liliana Esperanza
dc.contributor.orcidLiliana Silva-Igua [0000000244425209]
dc.coverage.countryColombia
dc.date.accessioned2025-09-05T15:22:55Z
dc.date.available2025-09-05T15:22:55Z
dc.date.issued2025-08-04
dc.descriptionilustraciones a color, diagramasspa
dc.description.abstractObjetivo: Identificar variantes germinales en 63 genes de susceptibilidad al cáncer en mujeres con carcinoma epitelial invasivo de mama, analizar su correlación con los subtipos tumorales y las vías de señalización o procesos biológicos relacionados. Diseño: Estudio observacional. Pacientes: Mujeres con carcinoma epitelial invasivo de mama, reclutadas entre 2019 y 2022. Lugar: Hospitales de Bogotá, Medellín, Cali, Bucaramanga, Valledupar y ciudades del Eje Cafetero. Metodología: Mediante secuenciación de exoma completo (Whole Exome Sequencing-WES), se estudiaron 400 mujeres con cáncer de mama, analizando variantes germinales con frecuencias alélicas poblacionales entre 1 % y 5 %, en 63 genes de susceptibilidad al cáncer. Se empleó Weighted Gene Correlation Network Analysis (WGCNA), así como pruebas estadísticas, para analizar y evaluar la correlación genotipo-fenotipo. Resultados: Se identificaron 73 variantes germinales en 29 genes, presentes en el 99,25% de las pacientes. El análisis WGCNA agrupó estos genes en módulos con variantes recurrentes implicadas en vías tumorigénicas. Se identificaron seis grupos, cada uno correlacionado con un subtipo molecular: Luminal A, Luminal B, HER2 enriquecido y triple negativo. Se encontraron correlaciones con significancia estadística entre variantes germinales y subtipos tumorales (valor p = 0,0470). La prueba de Chi-cuadrado de Pearson evidenció una relación estadísticamente significativa entre módulos y subtipos tumorales (valor p = 0,0009995). Conclusiones: Las variantes germinales en diversas vías tumorigénicas se correlacionan con los subtipos moleculares del cáncer de mama, lo que evidencia la influencia del componente poligénico en su heterogeneidad. WGCNA permitió una mejor comprensión de esta relación y facilitó la identificación de correlaciones genotipo-fenotipo. Esta metodología, poco utilizada, ofreció ventajas significativas sobre métodos tradicionales para el análisis de los datos genómicos (Texto tomado de la fuente).spa
dc.description.abstractObjective: To identify germline variants in 63 cancer susceptibility genes in women with invasive epithelial breast carcinoma, analyze their correlation with tumor subtypes and related signaling pathways or biological processes. Design: Observational study. Patients: Women with invasive epithelial breast carcinoma, recruited between 2019 and 2022. Location: Hospitals in Bogotá, Medellín, Cali, Bucaramanga, Valledupar, and cities in the Coffee Axis region. Methodology: Using whole-exome sequencing (WES), 400 women with breast cancer were studied, analyzing germline variants with population allele frequencies between 1% and 5% across 63 cancer susceptibility genes. Weighted Gene Correlation Network Analysis (WGCNA) was employed to analyze the correlation between genetic variants and statistical tests were used to evaluate the genotype-phenotype correlation. Results: Seventy-three germline variants were identified in 29 genes, present in 99.25% of patients. The WGCNA analysis grouped these genes into modules with recurrent variants involved in tumorigenic pathways. Six groups were identified, each correlated with a molecular subtype: Luminal A, Luminal B, HER2-enriched, and triple-negative. Statistically significant correlations were found between germline variants and tumor subtypes (p values = 0.0470). The Pearson chi-squared test showed a statistically significant relationship between modules and tumor subtypes (p = 0.0009995). Conclusions: Germline variants in various tumorigenic pathways correlate with molecular subtypes of breast cancer, highlighting the influence of the polygenic component on its heterogeneity. WGCNA allowed for a better understanding of this relationship and facilitated the identification of genotype-phenotype correlations. This methodology, underutilized, offered significant advantages over traditional methods for analyzing these data.eng
dc.description.degreelevelMaestría
dc.description.degreenameMagíster en Genética Humana
dc.description.methodsDesde el Centro de Investigación en Genética y Genómica de la Universidad del Rosario (CIGGUR), se desarrolló un estudio observacional retrospectivo en una población de mujeres con cáncer de mama, denominado “Genómica funcional para la descripción de mutaciones en el diagnóstico molecular del cáncer de seno no seleccionado en población colombiana”. Entre los objetivos del estudio matriz, se identificaron variantes germinales con frecuencias alélicas menores al 1%, considerando la realización de estudios funcionales subsecuentes para estas variantes de alta penetrancia. En este trabajo, se analizaron los datos obtenidos en esta cohorte de pacientes, incluyendo la identificación, descripción y análisis de las variantes encontradas en una frecuencia alélica poblacional entre el 1 % y 5 % (obtenida a partir de datos de exoma de gnomAD) en 63 genes de susceptibilidad al desarrollo de cáncer de mama, por medio de WES (Whole Exome Sequencing-WES).
dc.description.researchareaGenética Molecular del Cáncer de Mama
dc.format.extent127 páginas
dc.format.mimetypeapplication/pdf
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/88630
dc.language.isospa
dc.publisherUniversidad Nacional de Colombia
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotá
dc.publisher.facultyFacultad de Medicina
dc.publisher.placeBogotá, Colombia
dc.publisher.programBogotá - Medicina - Maestría en Genética Humana
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.licenseReconocimiento 4.0 Internacional
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.ddc610 - Medicina y salud::615 - Farmacología y terapéutica
dc.subject.ddc610 - Medicina y salud::616 - Enfermedades
dc.subject.decsNeoplasias de la Mamaspa
dc.subject.decsBreast Neoplasmseng
dc.subject.decsSecuenciación del Exomaspa
dc.subject.decsExome Sequencingeng
dc.subject.decsSecuenciación Completa del Genomaspa
dc.subject.decsWhole Genome Sequencingeng
dc.subject.decsAnálisis Mutacional de ADNspa
dc.subject.decsDNA Mutational Analysiseng
dc.subject.decsVariaciones en el Número de Copia de ADNspa
dc.subject.decsDNA Copy Number Variationseng
dc.subject.proposalVariantes germinalesspa
dc.subject.proposalSusceptibilidad al cáncerspa
dc.subject.proposalSecuenciación de exoma completo (WES)spa
dc.subject.proposalSubtipos moleculares de cáncer de mamaspa
dc.subject.proposalWeighted Gene Correlation Network Analysis (WGCNA)eng
dc.subject.proposalGermline variantseng
dc.subject.proposalCancer susceptibilityeng
dc.subject.proposalWhole exome sequencing (WES)eng
dc.subject.proposalBreast cancer molecular subtypeseng
dc.titleIdentificación de variantes germinales en 63 genes de susceptibilidad al cáncer en mujeres colombianas con cáncer de mama no seleccionadospa
dc.title.translatedIdentification of germline variants in 63 cancer susceptibility genes in unselected colombian women with breas cancereng
dc.typeTrabajo de grado - Maestría
dc.type.coarhttp://purl.org/coar/resource_type/c_bdcc
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.contentText
dc.type.driverinfo:eu-repo/semantics/masterThesis
dc.type.redcolhttp://purl.org/redcol/resource_type/TM
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dcterms.audience.professionaldevelopmentEstudiantes
dcterms.audience.professionaldevelopmentInvestigadores
dcterms.audience.professionaldevelopmentMaestros
dcterms.audience.professionaldevelopmentMedios de comunicación
dcterms.audience.professionaldevelopmentPúblico general
dcterms.audience.professionaldevelopmentResponsables políticos
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2

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Tesis de Maestría en Genética Humana
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Maestría en Genética Humana