Association of breast cancer DNA methylation profiles with hormone receptor status and response to tamoxifen

被引：276

作者：

Widschwendter, M

Siegmund, KD

Müller, HM

Fiegl, H

Marth, C

Müller-Holzner, E

Jones, PA

Laird, PW

机构：

[1] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Urol, Los Angeles, CA 90089 USA

[2] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA

[3] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA

[4] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Surg, Los Angeles, CA 90089 USA

[5] Univ Innsbruck, Univ Hosp, Dept Obstet & Gynecol, A-6020 Innsbruck, Austria

来源：

CANCER RESEARCH | 2004年 / 64卷 / 11期

关键词：

D O I：

10.1158/0008-5472.CAN-03-3852

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 a, 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.

引用

页码：3807 / 3813

页数：7

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