Please use this identifier to cite or link to this item: https://doi.org/10.3390/ijms19092553
Title: DNA methylation profiling of breast cancer cell lines along the epithelial mesenchymal spectrum—Implications for the choice of circulating tumour DNA methylation markers
Authors: Le A.V.-P.
Szaumkessel M.
Tan T.Z. 
Thiery J.-P. 
Thompson E.W.
Dobrovic A.
Keywords: Biomarkers
Breast cancer
Circulating tumour DNA
DNA methylation
Epithelial
Mesenchymal plasticity
Methylation-sensitive high-resolution melting (MS-HRM)
Minimal residual disease
Pyrosequencing
Issue Date: 2018
Publisher: MDPI AG
Citation: Le A.V.-P., Szaumkessel M., Tan T.Z., Thiery J.-P., Thompson E.W., Dobrovic A. (2018). DNA methylation profiling of breast cancer cell lines along the epithelial mesenchymal spectrum—Implications for the choice of circulating tumour DNA methylation markers. International Journal of Molecular Sciences 19 (9) : 2553. ScholarBank@NUS Repository. https://doi.org/10.3390/ijms19092553
Abstract: (1) Background: Epithelial–mesenchymal plasticity (EMP) is a dynamic process whereby epithelial carcinoma cells reversibly acquire morphological and invasive characteristics typical of mesenchymal cells. Identifying the methylation differences between epithelial and mesenchymal states may assist in the identification of optimal DNA methylation biomarkers for the blood-based monitoring of cancer. (2) Methods: Methylation-sensitive high-resolution melting (MS-HRM) was used to examine the promoter methylation status of a panel of established and novel markers in a range of breast cancer cell lines spanning the epithelial–mesenchymal spectrum. Pyrosequencing was used to validate the MS-HRM results. (3) Results: VIM, DKK3, and CRABP1 were methylated in the majority of epithelial breast cancer cell lines, while methylation of GRHL2, MIR200C, and CDH1 was restricted to mesenchymal cell lines. Some markers that have been used to assess minimal residual disease such as AKR1B1 and APC methylation proved to be specific for epithelial breast cell lines. However, RASSF1A, RAR?, TWIST1, and SFRP2 methylation was seen in both epithelial and mesenchymal cell lines, supporting their suitability for a multimarker panel. (4) Conclusions: Profiling DNA methylation shows a distinction between epithelial and mesenchymal phenotypes. Understanding how DNA methylation varies between epithelial and mesenchymal phenotypes may lead to more rational selection of methylation-based biomarkers for circulating tumour DNA analysis. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Source Title: International Journal of Molecular Sciences
URI: http://scholarbank.nus.edu.sg/handle/10635/152182
ISSN: 16616596
DOI: 10.3390/ijms19092553
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