Clinical ReportsExpression and subcellular localization of the bromodomain-containing protein 7 is a prognostic biomarker in breast cancerVivenza, Danielaa; Garrone, Ornellaa; Brizio, Rodolfob; Mantovani, Fiammac; Del Sal, Gianninoc; Merlano, Marcoa; Crook, Timd; Lo Nigro, Cristianaa,,eAuthor Information Departments of aOncology bPathology, S. Croce & Carle Teaching Hospital, Cuneo cMolecular Oncology Unit, LNCIB, Area Science Park, Trieste, Italy dDepartment of Oncology, St Luke’s Cancer Centre, Royal Surrey County Hospital, Guilford, UK eLaboratory Department, S. Croce & Carle Teaching Hospital, Cuneo, Italy Received 29 August 2019 Revised form accepted 14 December 2019 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.anti-cancerdrugs.com. Correspondence to Cristiana Lo Nigro, Laboratory Department, S. Croce & Carle Teaching Hospital, Via Coppino 26, 12100 Cuneo, Italy, Tel: +39 0171 616125; fax: +39 0171 641599; e-mail: firstname.lastname@example.org Anti-Cancer Drugs: April 2020 - Volume 31 - Issue 4 - p 423-430 doi: 10.1097/CAD.0000000000000897 Buy SDC Metrics Abstract Bromodomain-containing protein 7 (BRD7) is a member of the bromodomain-containing protein family. Previous studies suggest that BRD7 is predominantly localized in the nucleus, wherein it functions as a transcriptional regulator. Several lines of evidence imply a tumour suppressor function for BRD7. However, the importance of BRD7 in the pathogenesis of breast cancer is not well understood. We have investigated the expression, CpG island methylation and subcellular localization of BRD7 in breast cancer cell lines and clinical cases and thereby assessed its prognostic significance by correlating with clinical-pathological features and time-dependent clinical outcomes. We show that nuclear exclusion of BRD7 occurs commonly in breast cancer and is strongly associated with cases expressing wild-type p53. Moreover, clinical outcomes are significantly less favourable in cases with nuclear exclusion or loss of expression than those in which there is nuclear expression of BRD7. Methylation of the CpG island of BRD7 increases in breast cancer relative to normal breast tissue, but there is not an obvious correlation between methylation and reduced expression or between methylation and clinical outcomes. Overall, our results suggest that nuclear exclusion, rather than transcriptional silencing, is a common mechanism by which the tumour suppressor function of wild-type p53 is inhibited in breast cancer, and show that BRD7 is a promising candidate biomarker in breast cancer. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.