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

被引：126

作者：

Gu, Lei ^{[1
,2
]}

Frommel, Sandra C. ^{[3
,4
]}

Oakes, Christopher C. ^{[2
]}

Simon, Ronald ^{[5
]}

Grupp, Katharina ^{[5
]}

Gerig, Cristina Y. ^{[3
]}

Baer, Dominik ^{[3
]}

Robinson, Mark D. ^{[6
,7
]}

Baer, Constance ^{[2
]}

Weiss, Melanie ^{[2
]}

Gu, Zuguang ^{[1
]}

Schapira, Matthieu ^{[8
]}

Kuner, Ruprecht ^{[9
,10
]}

Sueltmann, Holger ^{[9
,10
]}

Provenzano, Maurizio ^{[11
]}

Yaspo, Marie-Laure ^{[12
]}

Brors, Benedikt ^{[1
]}

Korbel, Jan ^{[13
]}

Schlomm, Thorsten ^{[14
]}

Sauter, Guido ^{[5
]}

Eils, Roland ^{[1
,15
]}

Plass, Christoph ^{[2
]}

Santoro, Raffaella ^{[3
]}

机构：

[1] German Canc Res Ctr, Div Theoret Bioinformat, Heidelberg, Germany

[2] German Canc Res Ctr, Div Epigen & Canc Risk Factors, Heidelberg, Germany

[3] Univ Zurich, Inst Vet Biochem & Mol Biol, Zurich, Switzerland

[4] Univ Zurich, Life Sci Zurich Grad Sch, Mol Life Sci Program, Zurich, Switzerland

[5] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany

[6] Univ Zurich, Inst Mol Life Sci, Zurich, Switzerland

[7] Univ Zurich, SIB, Zurich, Switzerland

[8] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada

[9] German Canc Res Ctr, Unit Canc Genome Res, Heidelberg, Germany

[10] Natl Ctr Tumour Dis, Heidelberg, Germany

[11] Univ Zurich Hosp, Div Urol, Oncol Res Unit, CH-8091 Zurich, Switzerland

[12] Max Planck Inst Mol Genet, D-14195 Berlin, Germany

[13] EMBL, Genome Biol Unit, Heidelberg, Germany

[14] Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Clin, Hamburg, Germany

[15] Heidelberg Univ, Inst Pharm & Mol Biotechnol IPMB & BioQuant, Dept Bioinformat & Funct Genom, Heidelberg, Germany

来源：

NATURE GENETICS | 2015年 / 47卷 / 01期

基金：

瑞士国家科学基金会;

关键词：

RNA-POLYMERASE-I; GROUP PROTEIN EZH2; ANDROGEN RECEPTOR; HETEROCHROMATIN FORMATION; DNA METHYLATION; POLYCOMB; EXPRESSION; PROLIFERATION; CHROMATIN; COMPLEX;

D O I：

10.1038/ng.3165

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：22 / +

页数：12

共 69 条

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