Title
Hallmarks of aromatase inhibitor drug resistance revealed by epigenetic profiling in breast cancerHallmarks of aromatase inhibitor drug resistance revealed by epigenetic profiling in breast cancer
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Research group
Molecular Imaging, Pathology, Radiotherapy & Oncology (MIPRO)
Faculteit Geneeskunde
Publication type
article
Publication
Baltimore, Md :Waverly,
Subject
Human medicine
Source (journal)
Cancer research. - Baltimore, Md, 1941, currens
Volume/pages
73(2013):23, p. 6632-6641
ISSN
0008-5472
1538-7445
ISI
000327321700010
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Aromatase inhibitors are the major first-line treatment of estrogen receptor-positive breast cancer, but resistance to treatment is common. To date, no biomarkers have been validated clinically to guide subsequent therapy in these patients. In this study, we mapped the genome-wide chromatin-binding profiles of estrogen receptor alpha (ER alpha), along with the epigenetic modifications H3K4me3 and H3K27me3, that are responsible for determining gene transcription (n = 12). Differential binding patterns of ER alpha, H3K4me3, and H3K27me3 were enriched between patients with good or poor outcomes after aromatase inhibition. ER alpha and H3K27me3 patterns were validated in an additional independent set of breast cancer cases (n = 10). We coupled these patterns to array-based proximal gene expression and progression-free survival data derived from a further independent cohort of 72 aromatase inhibitor-treated patients. Through this approach, we determined that the ER alpha and H3K27me3 profiles predicted the treatment outcomes for first-line aromatase inhibitors. In contrast, the H3K4me3 pattern identified was not similarly informative. The classification potential of these genes was only partially preserved in a cohort of 101 patients who received first-line tamoxifen treatment, suggesting some treatment selectivity in patient classification. (C) 2013 AACR.
E-info
https://repository.uantwerpen.be/docman/iruaauth/711172/8486516.pdf
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