ESR1 Methylation Measured in Cell-Free DNA to Evaluate Endocrine Resistance in Metastatic Breast Cancer Patients

Manouk K. Bos; Teoman Deger; Stefan Sleijfer; John W.M. Martens; Saskia M. Wilting

doi:10.3390/ijms23105631

ESR1 Methylation Measured in Cell-Free DNA to Evaluate Endocrine Resistance in Metastatic Breast Cancer Patients

Manouk K. Bos^*, Teoman Deger, Stefan Sleijfer, John W.M. Martens, Saskia M. Wilting^*

^*Corresponding author for this work

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Abstract

ESR1 methylation was proposed as mechanism for endocrine resistance in metastatic breast cancer patients. To evaluate its potential as a minimally invasive biomarker, we investigated the feasibility of measuring ESR1 methylation in cell-free DNA (cfDNA) and its association with endocrine resistance. First, we provided evidence that demethylation in vitro restores ER expression. Subsequently, we found that ESR1 methylation in cfDNA was not enriched in endocrine-resistant versus endocrine-sensitive patients. Interestingly, we found a correlation between ESR1 methylation and age. Publicly available data confirm an age-related increase in ESR1 methylation in leukocytes, confounding the determination of the ESR1 methylation status of tumors using cfDNA.

Original language	English
Article number	5631
Journal	International Journal of Molecular Sciences
Volume	23
Issue number	10
DOIs	https://doi.org/10.3390/ijms23105631
Publication status	Published - 18 May 2022

Bibliographical note

Funding: This research was funded by the Dutch Cancer Society (project no. NKB-EMCR-2016-108154).

Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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title = "ESR1 Methylation Measured in Cell-Free DNA to Evaluate Endocrine Resistance in Metastatic Breast Cancer Patients",

abstract = "ESR1 methylation was proposed as mechanism for endocrine resistance in metastatic breast cancer patients. To evaluate its potential as a minimally invasive biomarker, we investigated the feasibility of measuring ESR1 methylation in cell-free DNA (cfDNA) and its association with endocrine resistance. First, we provided evidence that demethylation in vitro restores ER expression. Subsequently, we found that ESR1 methylation in cfDNA was not enriched in endocrine-resistant versus endocrine-sensitive patients. Interestingly, we found a correlation between ESR1 methylation and age. Publicly available data confirm an age-related increase in ESR1 methylation in leukocytes, confounding the determination of the ESR1 methylation status of tumors using cfDNA.",

author = "Bos, {Manouk K.} and Teoman Deger and Stefan Sleijfer and Martens, {John W.M.} and Wilting, {Saskia M.}",

note = "Funding: This research was funded by the Dutch Cancer Society (project no. NKB-EMCR-2016-108154). Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Martens, John W.M.

AU - Wilting, Saskia M.

PY - 2022/5/18

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ESR1 Methylation Measured in Cell-Free DNA to Evaluate Endocrine Resistance in Metastatic Breast Cancer Patients

Abstract

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