This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Martens, J. W.M. Articles by Foekens, J. A. Search for Related Content PubMed PubMed Citation Articles by Martens, J. W.M. Articles by Foekens, J. A.

Association of DNA Methylation of Phosphoserine Aminotransferase with Response to Endocrine Therapy in Patients with Recurrent Breast Cancer

¹ Department of Medical Oncology, Erasmus MC, Rotterdam, the Netherlands; ² Department of Biomedical Research and Development and Technology Development, Epigenomics AG, Berlin, Germany; ³ Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich; ⁴ Institute of Pathology, Technical University of Munich, Munich, Germany; and ⁵ GSF-Institute of Pathology, Center for Health and Environment, Munich-Neuherberg, Germany

Requests for reprints: Sabine Maier, Epigenomics AG, Praesidenteustraße 1, D-10178 Berlin, Germany. Phone: 49-30-24-345-344; Fax: 49-30-24-345-555; E-mail: sabine.maier{at}epigenomics.com.

To understand the biological basis of resistance to endocrine therapy is of utmost importance in patients with steroid hormone receptor–positive breast cancer. Not only will this allow us prediction of therapy success, it may also lead to novel therapies for patients resistant to current endocrine therapy. DNA methylation in the promoter regions of genes is a prominent epigenetic gene silencing mechanism that contributes to breast cancer biology. In the current study, we investigated whether promoter DNA methylation could be associated with resistance to endocrine therapy in patients with recurrent breast cancer. Using a microarray-based technology, the promoter DNA methylation status of 117 candidate genes was studied in a cohort of 200 steroid hormone receptor–positive tumors of patients who received the antiestrogen tamoxifen as first-line treatment for recurrent breast cancer. Of the genes analyzed, the promoter DNA methylation status of 10 genes was significantly associated with clinical outcome of tamoxifen therapy. The association of the promoter hypermethylation of the strongest marker, phosphoserine aminotransferase (PSAT1) with favorable clinical outcome was confirmed by an independent quantitative DNA methylation detection method. Furthermore, the extent of DNA methylation of PSAT1 was inversely associated with its expression at the mRNA level. Finally, also at the mRNA level, PSAT1 was a predictor of tamoxifen therapy response. Concluding, our work indicates that promoter hypermethylation and mRNA expression of PSAT1 are indicators of response to tamoxifen-based endocrine therapy in steroid hormone receptor–positive patients with recurrent breast cancer.

This article has been cited by other articles:

				T. van Agthoven, A. M. Sieuwerts, M. E. Meijer-van Gelder, M. P. Look, M. Smid, J. Veldscholte, S. Sleijfer, J. A. Foekens, and L. C.J. Dorssers Relevance of Breast Cancer Antiestrogen Resistance Genes in Human Breast Cancer Progression and Tamoxifen Resistance J. Clin. Oncol., February 1, 2009; 27(4): 542 - 549. [Abstract] [Full Text] [PDF]

				O. Hartmann, F. Spyratos, N. Harbeck, D. Dietrich, A. Fassbender, M. Schmitt, S. Eppenberger-Castori, V. Vuaroqueaux, F. Lerebours, K. Welzel, et al. DNA Methylation Markers Predict Outcome in Node-Positive, Estrogen Receptor-Positive Breast Cancer with Adjuvant Anthracycline-Based Chemotherapy Clin. Cancer Res., January 1, 2009; 15(1): 315 - 323. [Abstract] [Full Text] [PDF]

				D. Meijer, A. M Sieuwerts, M. P Look, T. van Agthoven, J. A Foekens, and L. C J Dorssers Fibroblast growth factor receptor 4 predicts failure on tamoxifen therapy in patients with recurrent breast cancer Endocr. Relat. Cancer, March 1, 2008; 15(1): 101 - 111. [Abstract] [Full Text] [PDF]

				D. Morvan and A. Demidem Metabolomics by Proton Nuclear Magnetic Resonance Spectroscopy of the Response to Chloroethylnitrosourea Reveals Drug Efficacy and Tumor Adaptive Metabolic Pathways Cancer Res., March 1, 2007; 67(5): 2150 - 2159. [Abstract] [Full Text] [PDF]

				K. Visvanathan, S. Sukumar, and N. E. Davidson Epigenetic Biomarkers and Breast Cancer: Cause for Optimism. Clin. Cancer Res., November 15, 2006; 12(22): 6591 - 6593. [Full Text] [PDF]

				M. Smid, Y. Wang, J. G.M. Klijn, A. M. Sieuwerts, Y. Zhang, D. Atkins, J. W.M. Martens, and J. A. Foekens Genes Associated With Breast Cancer Metastatic to Bone J. Clin. Oncol., May 20, 2006; 24(15): 2261 - 2267. [Abstract] [Full Text] [PDF]

				M. Bibikova, Z. Lin, L. Zhou, E. Chudin, E. W. Garcia, B. Wu, D. Doucet, N. J. Thomas, Y. Wang, E. Vollmer, et al. High-throughput DNA methylation profiling using universal bead arrays Genome Res., March 1, 2006; 16(3): 383 - 393. [Abstract] [Full Text] [PDF]

				A. M. Sieuwerts, M. E. Meijer-van Gelder, M. Timmermans, A. M.A.C. Trapman, R. R. Garcia, M. Arnold, A. J.W. Goedheer, H. Portengen, J. G.M. Klijn, and J. A. Foekens How ADAM-9 and ADAM-11 Differentially From Estrogen Receptor Predict Response to Tamoxifen Treatment in Patients with Recurrent Breast Cancer: a Retrospective Study Clin. Cancer Res., October 15, 2005; 11(20): 7311 - 7321. [Abstract] [Full Text] [PDF]