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

被引：127

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

[1] DNA Methylation Alterations Exhibit Intraindividual Stability and Interindividual Heterogeneity in Prostate Cancer Metastases [J].

Aryee, Martin J. ;

Liu, Wennuan ;

Engelmann, Julia C. ;

Nuhn, Philipp ;

Gurel, Meltem ;

Haffner, Michael C. ;

Esopi, David ;

Irizarry, Rafael A. ;

Getzenberg, Robert H. ;

Nelson, William G. ;

Luo, Jun ;

Xu, Jianfeng ;

Isaacs, William B. ;

Bova, G. Steven ;

Yegnasubramanian, Srinivasan .

SCIENCE TRANSLATIONAL MEDICINE, 2013, 5 (169)

[2] EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast [J].

Bachmann, IM ;

Halvorsen, OJ ;

Collett, K ;

Stefansson, IM ;

Straume, O ;

Haukaas, SA ;

Salvesen, HB ;

Otte, AP ;

Akslen, LA .

JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (02) :268-273

[3] EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer [J].

Adrian P. Bracken ;

Diego Pasini ;

Maria Capra ;

Elena Prosperini ;

Elena Colli ;

Kristian Helin .

The EMBO Journal, 2003, 22 (20) :5323-5335

[4] TMPRSS2-ERG- specific transcriptional modulation is associated with prostate cancer biomarkers and TGF-β signaling [J].

Brase, Jan C. ;

Johannes, Marc ;

Mannsperger, Heiko ;

Faelth, Maria ;

Metzger, Jennifer ;

Kacprzyk, Lukasz A. ;

Andrasiuk, Tatjana ;

Gade, Stephan ;

Meister, Michael ;

Sirma, Hueseyin ;

Sauter, Guido ;

Simon, Ronald ;

Schlomm, Thorsten ;

Beissbarth, Tim ;

Korf, Ulrike ;

Kuner, Ruprecht ;

Sueltmann, Holger .

BMC CANCER, 2011, 11

[5] Inhibition of RNA Polymerase I as a Therapeutic Strategy to Promote Cancer-Specific Activation of p53 [J].

Bywater, Megan J. ;

Poortinga, Gretchen ;

Sanij, Elaine ;

Hein, Nadine ;

Peck, Abigail ;

Cullinane, Carleen ;

Wall, Meaghan ;

Cluse, Leonie ;

Drygin, Denis ;

Anderes, Kenna ;

Huser, Nanni ;

Proffitt, Chris ;

Bliesath, Joshua ;

Haddach, Mustapha ;

Schwaebe, Michael K. ;

Ryckman, David M. ;

Rice, William G. ;

Schmitt, Clemens ;

Lowe, Scott W. ;

Johnstone, Ricky W. ;

Pearson, Richard B. ;

McArthur, Grant A. ;

Hannan, Ross D. .

CANCER CELL, 2012, 22 (01) :51-65

[6] Growth inhibitory effect of Kruppel-like factor 6 on human prostatic carcinoma and renal carcinoma cell lines [J].

Cheng, Xian-Feng ;

Li, Di ;

Zhuang, Min ;

Chen, Zhao-Yan ;

Lu, De-Xiang ;

Hattori, Toshio .

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 2008, 216 (01) :35-45

[7] Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].

Chin, L. ;

Meyerson, M. ;

Aldape, K. ;

Bigner, D. ;

Mikkelsen, T. ;

VandenBerg, S. ;

Kahn, A. ;

Penny, R. ;

Ferguson, M. L. ;

Gerhard, D. S. ;

Getz, G. ;

Brennan, C. ;

Taylor, B. S. ;

Winckler, W. ;

Park, P. ;

Ladanyi, M. ;

Hoadley, K. A. ;

Verhaak, R. G. W. ;

Hayes, D. N. ;

Spellman, Paul T. ;

Absher, D. ;

Weir, B. A. ;

Ding, L. ;

Wheeler, D. ;

Lawrence, M. S. ;

Cibulskis, K. ;

Mardis, E. ;

Zhang, Jinghui ;

Wilson, R. K. ;

Donehower, L. ;

Wheeler, D. A. ;

Purdom, E. ;

Wallis, J. ;

Laird, P. W. ;

Herman, J. G. ;

Schuebel, K. E. ;

Weisenberger, D. J. ;

Baylin, S. B. ;

Schultz, N. ;

Yao, Jun ;

Wiedemeyer, R. ;

Weinstein, J. ;

Sander, C. ;

Gibbs, R. A. ;

Gray, J. ;

Kucherlapati, R. ;

Lander, E. S. ;

Myers, R. M. ;

Perou, C. M. ;

McLendon, Roger .

NATURE, 2008, 455 (7216) :1061-1068

[8] Hypermethylation of CpG island loci and hypomethylation of LINE-I and Alu repeats in prostate adenocarcinoma and their relationship to clinicopathological features [J].

Cho, N-Y ;

Kim, B-H ;

Yoo, E. J. ;

Moon, K. C. ;

Cho, Y-M ;

Kim, D. ;

Kang, G. H. .

JOURNAL OF PATHOLOGY, 2007, 211 (03) :269-277

[9] miRGator v3.0: a microRNA portal for deep sequencing, expression profiling and mRNA targeting [J].

Cho, Sooyoung ;

Jang, Insu ;

Jun, Yukyung ;

Yoon, Suhyeon ;

Ko, Minjeong ;

Kwon, Yeajee ;

Choi, Ikjung ;

Chang, Hyeshik ;

Ryu, Daeun ;

Lee, Byungwook ;

Kim, V. Narry ;

Kim, Wankyu ;

Lee, Sanghyuk .

NUCLEIC ACIDS RESEARCH, 2013, 41 (D1) :D252-D257

[10] Prospective identification of tumorigenic prostate cancer stem cells [J].

Collins, AT ;

Berry, PA ;

Hyde, C ;

Stower, MJ ;

Maitland, NJ .

CANCER RESEARCH, 2005, 65 (23) :10946-10951

← 1 2 3 4 5 6 7 →