Characterizing steroid hormone receptor chromatin binding landscapes in male and female breast cancer

Tesa M. Severson, Yongsoo Kim, Stacey E. P. Joosten, Karianne Schuurman, Petra van der Groep, Cathy B. Moelans, Natalie D. ter Hoeve, Quirine F. Manson, John W. Martens, Carolien H. M. van Deurzen, Ellis Barbe, Ingrid Hedenfalk, Peter Bult, Vincent T. H. B. M. Smit, Sabine C. Linn, Paul J. van Diest, Lodewyk Wessels and Wilbert Zwart ()
Additional contact information
Tesa M. Severson: Oncode Institute, Netherlands Cancer Institute
Yongsoo Kim: Oncode Institute, Netherlands Cancer Institute
Stacey E. P. Joosten: Oncode Institute, Netherlands Cancer Institute
Karianne Schuurman: Oncode Institute, Netherlands Cancer Institute
Petra van der Groep: University Medical Center
Cathy B. Moelans: University Medical Center
Natalie D. ter Hoeve: University Medical Center
Quirine F. Manson: University Medical Center
John W. Martens: Dutch Breast Cancer Research Group, (BOOG Study Center)
Carolien H. M. van Deurzen: Dutch Breast Cancer Research Group, (BOOG Study Center)
Ellis Barbe: Dutch Breast Cancer Research Group, (BOOG Study Center)
Ingrid Hedenfalk: Lund University
Peter Bult: Radboud University Medical Center
Vincent T. H. B. M. Smit: Dutch Breast Cancer Research Group, (BOOG Study Center)
Sabine C. Linn: University Medical Center
Paul J. van Diest: University Medical Center
Lodewyk Wessels: Oncode Institute, Netherlands Cancer Institute
Wilbert Zwart: Oncode Institute, Netherlands Cancer Institute

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Male breast cancer (MBC) is rare and poorly characterized. Like the female counterpart, most MBCs are hormonally driven, but relapse after hormonal treatment is also noted. The pan-hormonal action of steroid hormonal receptors, including estrogen receptor alpha (ERα), androgen receptor (AR), progesterone receptor (PR), and glucocorticoid receptor (GR) in this understudied tumor type remains wholly unexamined. This study reveals genomic cross-talk of steroid hormone receptor action and interplay in human tumors, here in the context of MBC, in relation to the female disease and patient outcome. Here we report the characterization of human breast tumors of both genders for cistromic make-up of hormonal regulation in human tumors, revealing genome-wide chromatin binding landscapes of ERα, AR, PR, GR, FOXA1, and GATA3 and enhancer-enriched histone mark H3K4me1. We integrate these data with transcriptomics to reveal gender-selective and genomic location-specific hormone receptor actions, which associate with survival in MBC patients.

Date: 2018
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DOI: 10.1038/s41467-018-02856-2

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