BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its 
overexpression predicts disease recurrence

Gu, L.; Frommel, S. C.; Oakes, C. C.; Simon, R.; Grupp, K.; Gerig, C. Y.; Bar, D.; Robinson, M. D.; Baer, C.; Weiss, M.; Gu, Z.; Schapira, M.; Kuner, R.; Sultmann, H.; Provenzano, M.; Cancer, Icgc Project on Early Onset Prostate; Yaspo, M. L.; Brors, B.; Korbel, J.; Schlomm, T.; Sauter, G.; Eils, R.; Plass, C.; Santoro, R.

doi:10.1038/ng.3165

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BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence

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Yaspo, M. L.
Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Gu, L., Frommel, S. C., Oakes, C. C., Simon, R., Grupp, K., Gerig, C. Y., et al. (2015). BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence. Nature Genetics, 47(1), 22-30. doi:10.1038/ng.3165.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002A-5FD7-9

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.