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Please use this identifier to cite or link to this item: http://hdl.handle.net/10481/31170

Title: ESR1 gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients
Authors: Martínez-Galán, Joaquina
Torres-Torres, Blanca
Núñez, María Isabel
López-Peñalver, Jesús
Moral Ávila, Rosario del
Ruiz de Almodóvar, Mariano
Menjón, Salomón
Concha, Ángel
Chamorro, Clara
Ríos-Arrabal, Sandra
Delgado, Juan Ramón
Issue Date: 2014
Abstract: [Background] Tumor 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. [Methods] Patients (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). [Results] Our 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. [Conclusion] Silencing, 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.
Sponsorship: The study was funded, in part, by a grant from the Ministerio de Educación y Ciencia (CICYT: SAF 2004–00889).
Publisher: Biomed Central
Keywords: Breast cancer
Methylation
Luminal phenotypes
URI: http://hdl.handle.net/10481/31170
ISSN: 1471-2407
Rights : Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
Citation: Martínez-Galán, J.; 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, 14: 59 (2014). [http://hdl.handle.net/10481/31170]
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