Biomarcadores genómicos asociados a cáncer pulmonar, en células epiteliales de esputo inducido
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Fecha
2016
Autores
Profesor/a Guía
Facultad/escuela
Idioma
es
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Universidad Andrés Bello
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Licencia CC
Licencia CC
Resumen
El cáncer de pulmón (CAP) es la primera causa de muerte por cáncer a nivel mundial y
en Chile, es la segunda causa de muerte por cáncer. Estas cifras se relacionan con un
diagnóstico tardío, por carencia de un método de diagnóstico en etapas tempranas.
Más del 75% de los pacientes diagnosticados con CAP se encuentran en los estadios III
ó IV, etapas que tienen menos de un 15% de sobrevida a los 5 años. Para el
diagnóstico en estadios tempranos, la sobrevida alcanza el 70% a los 5 años. Por lo
tanto, el desarrollo de tecnologías no invasivas asociadas a un diagnóstico temprano,
podrían contribuir con un aumento en la sobrevida de los pacientes con CAP; por
diagnóstico en etapas tempranas de la enfermedad. En este punto, marcadores
genómicos en muestras de esputo podrían resultar en herramientas complementarias
efectivas para el diagnóstico de CAP.
Hipótesis: Las células epiteliales pulmonares, presentes en el esputo de pacientes con
cáncer pulmonar, presentan alteraciones del número de copias (ANC) asociadas a la
patología y al tipo histológico.
Objetivos: Determinar Alteraciones en el Número de Copias (ANC) en el ADN
genómico de células epiteliales de esputo de pacientes con Cáncer Pulmonar del tipo
escamoso y adenocarcinoma.
Métodos: Se obtienen muestras de esputo y de sangre de 8 pacientes con cáncer
pulmonar y de 8 individuos sanos. Las muestras de esputo fueron procesadas para
separar las células contenidas en el esputo de acuerdo a su tamaño a modo de
enriquecimiento de células epiteliales. Tanto el ADN de las células epiteliales del esputo
como el de sangre periférica, se sometieron a experimentos de array-CGH.
Resultados: El análisis realizado de las ANC, dio como resultado un listado de genes
con alteraciones asociadas a CAP, así como también un listado de genes alterados
exclusivamente para los tipos histológicos Adenocarcinoma y Carcinoma Escamoso.
Conclusión y proyecciones: Las muestras de esputo contienen células cancerígenas
adecuadas para el análisis genético. Los genes identificados se podrían utilizar para
posteriores análisis de biomarcadores. Los resultados serán un aporte en la generación
de un método de diagnóstico complementario no invasivo que contribuya a la detección
temprana de CAP, y con ello mejorar a la sobrevida de los pacientes.
Lung cancer (LC) is the leading cause of cancer death worldwide and in Chile it is the second leading cause of cancer death. These situation are related to a late diagnosis, due to the lack of a diagnostic method in the early stages. More than 75% of patients diagnosed with LC are in stages III or IV, stages that have less than 15% of survival at 5 years. For the diagnosis in the early stages, survival reaches 70% at 5 years. Therefore, the development of non-invasive technologies associated with an early diagnosis, could contribute with an increase in the survival of patients with LC; by diagnosis in the early stages of the disease. At this point, genomic markers in sputum samples could result in effective complementary tools for the diagnosis of LC. Hypothesis: Pulmonary epithelial cells, present in the sputum of patients with lung cancer, present Copies Number Alterations (CNA) associated with pathology and histological type. Objectives: To determine Copies Number Alterations (CNA) in genomic DNA from sputum epithelial cells of patients with squamous cell lung cancer and adenocarcinoma. Methods: Sputum and blood samples were obtained from 8 lung cancer patients and 8 healthy individuals. The sputum samples were processed to separate the cells contained in the sputum according to their size as enrichment of epithelial cells. Both DNA from the sputum epithelial cells and DNA from peripheral blood cells were subjected to array-CGH experiments. Results: CNA analysis resulted in a list of genes with LC-associated alterations as well as a list of genes altered exclusively for the histological types Adenocarcinoma and Squamous Carcinoma. Conclusion and projections: Sputum samples contain cancer cells suitable for genetic analysis. The identified genes could be used for further analysis of biomarkers. The results will be a contribution in the generation of a non-invasive complementary diagnostic method that contributes to the early detection of LC, and thus improve patient survival.
Lung cancer (LC) is the leading cause of cancer death worldwide and in Chile it is the second leading cause of cancer death. These situation are related to a late diagnosis, due to the lack of a diagnostic method in the early stages. More than 75% of patients diagnosed with LC are in stages III or IV, stages that have less than 15% of survival at 5 years. For the diagnosis in the early stages, survival reaches 70% at 5 years. Therefore, the development of non-invasive technologies associated with an early diagnosis, could contribute with an increase in the survival of patients with LC; by diagnosis in the early stages of the disease. At this point, genomic markers in sputum samples could result in effective complementary tools for the diagnosis of LC. Hypothesis: Pulmonary epithelial cells, present in the sputum of patients with lung cancer, present Copies Number Alterations (CNA) associated with pathology and histological type. Objectives: To determine Copies Number Alterations (CNA) in genomic DNA from sputum epithelial cells of patients with squamous cell lung cancer and adenocarcinoma. Methods: Sputum and blood samples were obtained from 8 lung cancer patients and 8 healthy individuals. The sputum samples were processed to separate the cells contained in the sputum according to their size as enrichment of epithelial cells. Both DNA from the sputum epithelial cells and DNA from peripheral blood cells were subjected to array-CGH experiments. Results: CNA analysis resulted in a list of genes with LC-associated alterations as well as a list of genes altered exclusively for the histological types Adenocarcinoma and Squamous Carcinoma. Conclusion and projections: Sputum samples contain cancer cells suitable for genetic analysis. The identified genes could be used for further analysis of biomarkers. The results will be a contribution in the generation of a non-invasive complementary diagnostic method that contributes to the early detection of LC, and thus improve patient survival.
Notas
Tesis (Ingeniero en Biotecnología)
Palabras clave
Marcadores Genéticos, Cáncer del Pulmón