1. BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence
- Author
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Gu Lei, Frommel Sandra C, Oakes Christopher C, Simon Ronald, Grupp Katharina, Gerig Cristina Y, Bär Dominik, Robinson Mark D, Baer Constance, Weiss Melanie, Gu Zuguang, Schapira Matthieu, Kuner Ruprecht, Sültmann Holger, Provenzano Maurizio, ICGC Project on Early Onset Prostate Cancer, Yaspo Marie-Laure, Brors Benedikt, Korbel Jan, Schlomm Thorsten, Sauter Guido, Eils Roland, Plass Christoph, Santoro Raffaella, University of Zurich, and Santoro, Raffaella
- Subjects
Male ,Biochemical recurrence ,Chromosomal Proteins, Non-Histone ,610 Medicine & health ,Adenocarcinoma ,Epigenetic Repression ,Biology ,Metastasis ,Prostate cancer ,1311 Genetics ,Cell Line, Tumor ,Protein Interaction Mapping ,Biomarkers, Tumor ,Genetics ,medicine ,Humans ,Enhancer of Zeste Homolog 2 Protein ,Neoplasm Invasiveness ,RNA, Neoplasm ,Epigenetics ,Neoplasm Metastasis ,Epigenomics ,EZH2 ,Polycomb Repressive Complex 2 ,Prostatic Neoplasms ,DNA Methylation ,Prognosis ,medicine.disease ,10226 Department of Molecular Mechanisms of Disease ,10124 Institute of Molecular Life Sciences ,Neoplasm Proteins ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,10062 Urological Clinic ,RNA, Ribosomal ,DNA methylation ,Cancer research ,570 Life sciences ,biology ,CpG Islands ,Cell Division ,Follow-Up Studies - Abstract
Prostate cancer is driven by a combination of genetic and/or epigenetic alterations. Epigenetic alterations are frequently observed in all human cancers, yet how aberrant epigenetic signatures are established is poorly understood. Here we show that the gene encoding BAZ2A (TIP5), a factor previously implicated in epigenetic rRNA gene silencing, is overexpressed in prostate cancer and is paradoxically involved in maintaining prostate cancer cell growth, a feature specific to cancer cells. BAZ2A regulates numerous protein-coding genes and directly interacts with EZH2 to maintain epigenetic silencing at genes repressed in metastasis. BAZ2A overexpression is tightly associated with a molecular subtype displaying a CpG island methylator phenotype (CIMP). Finally, high BAZ2A levels serve as an independent predictor of biochemical recurrence in a cohort of 7,682 individuals with prostate cancer. This work identifies a new aberrant role for the epigenetic regulator BAZ2A, which can also serve as a useful marker for metastatic potential in prostate cancer.
- Published
- 2015