RT Journal Article
T1 ESR1 gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients.
A1 Martínez-Galán, Joaquina
A1 Torres-Torres, Blanca
A1 Núñez, María Isabel
A1 López-Peñalver, Jesús
A1 Del Moral, Rosario
A1 Ruiz De Almodóvar, José Mariano
A1 Menjón, Salomón
A1 Concha, Angel
A1 Chamorro, Clara
A1 Ríos, Sandra
A1 Delgado, Juan Ramón
K1 Breast cancer
K1 Methylation
K1 Luminal phenotypes
K1 Metilación
K1 Neoplasias de la Mama
K1 Antineoplásicos Hormonales
K1 Receptores Estrogénicos
K1 Metilación de ADN
K1 Epigénesis Genética
K1 Femenino
AB BACKGROUNDTumor expression of estrogen receptor (ER) is an important marker of prognosis, and is predictive of response to endocrine therapy in breast cancer. Several studies have observed that epigenetic events, such methylation of cytosines and deacetylation of histones, are involved in the complex mechanisms that regulate promoter transcription. However, the exact interplay of these factors in transcription activity is not well understood. In this study, we explored the relationship between ER expression status in tumor tissue samples and the methylation of the 5' CpG promoter region of the estrogen receptor gene (ESR1) isolated from free circulating DNA (fcDNA) in plasma samples from breast cancer patients.METHODSPatients (n = 110) with non-metastatic breast cancer had analyses performed of ER expression (luminal phenotype in tumor tissue, by immunohistochemistry method), and the ESR1-DNA methylation status (fcDNA in plasma, by quantitative methylation specific PCR technique).RESULTSOur results showed a significant association between presence of methylated ESR1 in patients with breast cancer and ER negative status in the tumor tissue (p = 0.0179). There was a trend towards a higher probability of ESR1-methylation in those phenotypes with poor prognosis i.e. 80% of triple negative patients, 60% of HER2 patients, compared to 28% and 5.9% of patients with better prognosis such as luminal A and luminal B, respectively.CONCLUSIONSilencing, by methylation, of the promoter region of the ESR1 affects the expression of the estrogen receptor protein in tumors of breast cancer patients; high methylation of ESR1-DNA is associated with estrogen receptor negative status which, in turn, may be implicated in the patient's resistance to hormonal treatment in breast cancer. As such, epigenetic markers in plasma may be of interest as new targets for anticancer therapy, especially with respect to endocrine treatment.
PB BioMed Central
YR 2014
FD 2014-02-04
LK http://hdl.handle.net/10668/1634
UL http://hdl.handle.net/10668/1634
LA en
NO Martínez-Galán J, Torres-Torres B, Núñez MI, López-Peñalver J, Del Moral R, Ruiz De Almodóvar JM, et al. ESR1 gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients. BMC Cancer. 2014; 14:59
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 12, 2025