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Nat Genet. 2015 Jan;47(1):22-30. doi: 10.1038/ng.3165. Epub 2014 Dec 8.

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

Author information

1
1] Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany. [2] Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany.
2
1] Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich, Switzerland. [2] Molecular Life Science Program, Life Science Zurich Graduate School, University of Zurich, Zurich, Switzerland.
3
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany.
4
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
5
Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich, Switzerland.
6
1] Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland. [2] Swiss Institute of Bioinformatics (SIB), University of Zurich, Zurich, Switzerland.
7
Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
8
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
9
Unit of Cancer Genome Research, German Cancer Research Center (DKFZ) and National Center of Tumour Diseases, Heidelberg, Germany.
10
Oncology Research Unit, Division of Urology, University Hospital of Zurich, Zurich, Switzerland.
11
Max Planck Institute for Molecular Genetics, Berlin, Germany.
12
Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
13
Martini Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
14
1] Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany. [2] Department for Bioinformatics and Functional Genomics, Institute for Pharmacy and Molecular Biotechnology (IPMB) and BioQuant, Heidelberg University, Heidelberg, Germany.

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.

PMID:
25485837
DOI:
10.1038/ng.3165
[Indexed for MEDLINE]

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