title: BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence.
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.
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Gu
authors.affiliation: 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.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Frommel
authors.affiliation: Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Oakes
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Grupp
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich, Switzerland.
authors.forename: Cristina Y
authors.initials: CY
authors.lastname: Gerig
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich, Switzerland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Bär
authors.affiliation: 1] Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland. [2] Swiss Institute of Bioinformatics (SIB), University of Zurich, Zurich, Switzerland.
authors.forename: Mark D
authors.identifier: 0000000230485518
authors.initials: MD
authors.lastname: Robinson
authors.affiliation: Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Constance
authors.initials: C
authors.lastname: Baer
authors.affiliation: Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Weiss
authors.affiliation: Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Zuguang
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Schapira
authors.affiliation: Unit of Cancer Genome Research, German Cancer Research Center (DKFZ) and National Center of Tumour Diseases, Heidelberg, Germany.
authors.forename: Ruprecht
authors.initials: R
authors.lastname: Kuner
authors.affiliation: Unit of Cancer Genome Research, German Cancer Research Center (DKFZ) and National Center of Tumour Diseases, Heidelberg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Sültmann
authors.affiliation: Oncology Research Unit, Division of Urology, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Provenzano
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Yaspo
authors.affiliation: Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Brors
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
authors.forename: Jan
authors.identifier: 0000000227983794
authors.initials: J
authors.lastname: Korbel
authors.affiliation: Martini Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: 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.
authors.forename: Roland
authors.initials: R
authors.lastname: Eils
authors.affiliation: Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich, Switzerland.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Santoro
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics; D002455:Cell Division; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018899:CpG Islands; D019175:DNA Methylation; D000071221:Enhancer of Zeste Homolog 2 Protein; D063185:Epigenetic Repression; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D063151:Polycomb Repressive Complex 2 / Q000502:physiology; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025941:Protein Interaction Mapping; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012335:RNA, Ribosomal / Q000096:biosynthesis; D015854:Up-Regulation; D000092468:Bromodomain Containing Proteins
chemical_list: D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D000071221:Enhancer of Zeste Homolog 2 Protein; D009363:Neoplasm Proteins; D063151:Polycomb Repressive Complex 2; D012334:RNA, Neoplasm; D012335:RNA, Ribosomal; C436708:BAZ2A protein, human; D000092468:Bromodomain Containing Proteins; C498409:EZH2 protein, human