Selección de biomarcadores epigenéticos en biopsias líquidas de pacientes con cáncer de mama
Breast cancer is the principal cause of death from tumors in women in Argentina, producing almost 5600 deaths per year. Until 2014, Mendoza and La Pampa had the highest mortality rates in Argentina. The tumorigenic process is characterized by the acquisition of genetic and epigenetic alterations ove...
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| Autores principales: | , , , , |
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| Publicado: |
2019
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| Acceso en línea: | https://bdigital.uncu.edu.ar/fichas.php?idobjeto=14897 |
| Sumario: | Breast cancer is the principal cause of death from tumors in women in Argentina, producing almost 5600 deaths per year. Until 2014, Mendoza and La Pampa had the highest mortality rates in Argentina. The tumorigenic process is characterized by the acquisition of genetic and epigenetic alterations over time. Aberrant promoter methylation of tumor suppressor genes has been described as part of mammary tumorigenesis since early tumor stages.Recently, the study of liquid biopsies was increased in cancer patients in different research centers. The study consists in the isolation of different species derived from tumors, among which circulating tumor DNA (cDNA) is one of the most studied. In this specie can be detected, variation in the number of gene copies, methylation of CpG sites, etc. The alterations found can later be defined as biomarkers that could finally considered in clinical decisions.We studied the aberrant methylation of tumor suppressor genes in human mammary carcinomas since 2005. To date we have analyzed the methylation status of approximately 100 CpG sites in a bank of around 250 samples derived from fresh mammary tumors, margins of surgical resection, lymph nodes and benign lesions of the breast. We have detected that certain CpG sites located in promoters and first exons of the genes present high methylation frequencies in mammary tumors of our region.In this project we propose to scale up and analyze 450,000 CpG sites in harmonized in silico databases (GDC-TCGA) through the use of bioinformatics tools. We hope to find sensitive and specific biomarkers for detection in liquid biopsies. We are going to applied a novel technique for the detection of alterations in cDNA, called methyl-specific digital PCR which is based on TaqMan probes. This technique presents the advantage that it could be transferred and implemented in the clinic area. Our group maintains a consolidated collaboration with medical pathologists, mastologists and oncologists at the Instituto Gineco Mamario de Mendoza. This center will provide us the blood samples from patients. On the other hand, we have an active collaboration of "Quinto impacto" company that will participate in the development of bioinformatics tools. |
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