EZH2 is overexpressed in breast tumors with a BRCA1-like DNA copy number profile

• Main Authors: Puppe, J, Opdam, M, Jozwiak, K, Schouten, PC, Rodenhuis, S, Hauptmann, M, Hahnen, E, Mallmann, P, Schmutzler, R, Linn, S, Jonkers, J
• Format: Conference Proceeding
• Language: English
• ISSN: 0016-5751; 1438-8804
• DOI: 10.1055/s-0036-1592820

Purpose: The polycomb group protein EZH2 is an epigenetic repressor and overexpression of EZH2 is associated with highly aggressive types of breast cancer. Human BRCA1-mutated breast tumors carry a specific DNA copy-number signature (“BRCA1-like”) which is also found in tumors with a loss of BRCA1 function by other mechanism such as BRCA1-promoter methylation. Here, we explored whether EZH2 is overexpressed in human BRCA1-like breast tumors. Patients and methods: In our study we have analyzed the abundance of EZH2 expression using immunohistochemistry in a cohort of nearly 400 patients. We classified copy-number profiles by array comparative genomic hybridization (aCGH) to be BRCA1-like or non-BRCA1-like in 160 patients and examined its association with EZH2 expression. Results: In total, 266 tumors were considered to be EZH2 positive. EZH2 expression was significantly higher in triple-negative breast tumors compared to hormone receptor positive breast tumors. Out of the 160 tumors classified by aCGH 36 samples show a BRCA1-like profile. The group of BRCA1-like tumors included 14 samples with a BRCA1-promoter methylation and 6 samples with a BRCA1-mutation. The highest EZH2 expression was found in tumors classified as BRCA1-like when compared to non-BRCA1-like breast tumors. Conclusion: Our findings demonstrate that EZH2 is significantly higher expressed in breast tumors with a BRCA1-like DNA copy number profile indicating that EZH2 overexpression is not restricted to BRCA1-mutation status. Therefore, EZH2 should be further examined as prognostic biomarker and potential target for breast tumors identified by the BRCA1-like classifier.