Association of Breast Cancer DNA Methylation Profiles with Hormone Receptor Status and Response to Tamoxifen
2004; American Association for Cancer Research; Volume: 64; Issue: 11 Linguagem: Inglês
10.1158/0008-5472.can-03-3852
ISSN1538-7445
AutoresMartin Widschwendter, Kimberly D. Siegmund, Hannes Müller, Heidi Fiegl, Christian Marth, Elisabeth Müller‐Holzner, Peter A. Jones, Peter W. Laird,
Tópico(s)Genomics and Chromatin Dynamics
ResumoAbstract We have generated DNA methylation profiles of 148 human breast tumors and found significant differences in hormone receptor (HR) status between clusters of DNA methylation profiles. Of 35 DNA methylation markers analyzed, the ESR1 gene, encoding estrogen receptor α, proved to be the best predictor of progesterone receptor status, whereas methylation of the PGR gene, encoding progesterone receptor, was the best predictor of estrogen receptor status. ESR1 methylation outperformed HR status as a predictor of clinical response in patients treated with the antiestrogen tamoxifen, whereas promoter methylation of the CYP1B1 gene, encoding a tamoxifen- and estradiol-metabolizing cytochrome P450, predicted response differentially in tamoxifen-treated and nontamoxifen-treated patients. High levels of promoter methylation of the ARHI gene, encoding a RAS-related small G-protein, were strongly predictive of good survival in patients who had not received tamoxifen therapy. Our results reveal an as yet unrecognized degree of interaction between DNA methylation and HR biology in breast cancer cells and suggest potentially clinically useful novel DNA methylation predictors of response to hormonal and non-hormonal breast cancer therapy.
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