Expression of Polycomb Targets Predicts Breast Cancer Prognosis

被引：33

作者：

Jene-Sanz, Alba ^{[1
,2
]}

Varaljai, Renata ^{[2
]}

Vilkova, Alexandra V. ^{[2
]}

Khramtsova, Galina F. ^{[3
]}

Khramtsov, Andrey I. ^{[4
]}

Olopade, Olufunmilayo I. ^{[3
]}

Lopez-Bigas, Nuria ^{[1
,5
]}

Benevolenskaya, Elizaveta V. ^{[2
]}

机构：

[1] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Res Unit Biomed Informat, Barcelona, Spain

[2] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA

[3] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA

[4] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[5] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2013年 / 33卷 / 19期

基金：

美国国家卫生研究院;

关键词：

EMBRYONIC STEM-CELLS; GENE-EXPRESSION; DEVELOPMENTAL REGULATORS; PROSTATE-CANCER; EZH2; EXPRESSION; HUMAN GENOME; DATA SETS; IDENTIFICATION; SUBTYPES; TUMORS;

D O I：

10.1128/MCB.00426-13

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Global changes in the epigenome are increasingly being appreciated as key events in cancer progression. The pathogenic role of enhancer of zeste homolog 2 (EZH2) has been connected to its histone 3 lysine 27 (H3K27) methyltransferase activity and gene repression; however, little is known about relationship of changes in expression of EZH2 target genes to cancer characteristics and patient prognosis. Here we show that through expression analysis of genomic regions with H3K27 trimethylation (H3K27me3) and EZH2 binding, breast cancer patients can be stratified into good and poor prognostic groups independent of known cancer gene signatures. The EZH2-bound regions were downregulated in tumors characterized by aggressive behavior, high expression of cell cycle genes, and low expression of developmental and cell adhesion genes. Depletion of EZH2 in breast cancer cells significantly increased expression of the top altered genes, decreased proliferation, and improved cell adhesion, indicating a critical role played by EZH2 in determining the cancer phenotype.

引用

页码：3951 / 3961

页数：11

共 55 条

[1]

Increased risk for distant metastasis in patients with familial early-stage breast cancer and high EZH2 expression [J].

Alford, Sharon Hensley ;

Toy, Katherine ;

Merajver, Sofia D. ;

Kleer, Celina G. .

BREAST CANCER RESEARCH AND TREATMENT, 2012, 132 (02) :429-437

[2]

Pyicos: a versatile toolkit for the analysis of high-throughput sequencing data [J].

Althammer, Sonja ;

Gonzalez-Vallinas, Juan ;

Ballare, Cecilia ;

Beato, Miguel ;

Eyras, Eduardo .

BIOINFORMATICS, 2011, 27 (24) :3333-3340

[3]

Gene Ontology: tool for the unification of biology [J].

Ashburner, M ;

Ball, CA ;

Blake, JA ;

Botstein, D ;

Butler, H ;

Cherry, JM ;

Davis, AP ;

Dolinski, K ;

Dwight, SS ;

Eppig, JT ;

Harris, MA ;

Hill, DP ;

Issel-Tarver, L ;

Kasarskis, A ;

Lewis, S ;

Matese, JC ;

Richardson, JE ;

Ringwald, M ;

Rubin, GM ;

Sherlock, G .

NATURE GENETICS, 2000, 25 (01) :25-29

[4]

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

[5]

An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors [J].

Ben-Porath, Ittai ;

Thomson, Matthew W. ;

Carey, Vincent J. ;

Ge, Ruping ;

Bell, George W. ;

Regev, Aviv ;

Weinberg, Robert A. .

NATURE GENETICS, 2008, 40 (05) :499-507

[6]

CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[7]

Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project [J].

Birney, Ewan ;

Stamatoyannopoulos, John A. ;

Dutta, Anindya ;

Guigo, Roderic ;

Gingeras, Thomas R. ;

Margulies, Elliott H. ;

Weng, Zhiping ;

Snyder, Michael ;

Dermitzakis, Emmanouil T. ;

Stamatoyannopoulos, John A. ;

Thurman, Robert E. ;

Kuehn, Michael S. ;

Taylor, Christopher M. ;

Neph, Shane ;

Koch, Christoph M. ;

Asthana, Saurabh ;

Malhotra, Ankit ;

Adzhubei, Ivan ;

Greenbaum, Jason A. ;

Andrews, Robert M. ;

Flicek, Paul ;

Boyle, Patrick J. ;

Cao, Hua ;

Carter, Nigel P. ;

Clelland, Gayle K. ;

Davis, Sean ;

Day, Nathan ;

Dhami, Pawandeep ;

Dillon, Shane C. ;

Dorschner, Michael O. ;

Fiegler, Heike ;

Giresi, Paul G. ;

Goldy, Jeff ;

Hawrylycz, Michael ;

Haydock, Andrew ;

Humbert, Richard ;

James, Keith D. ;

Johnson, Brett E. ;

Johnson, Ericka M. ;

Frum, Tristan T. ;

Rosenzweig, Elizabeth R. ;

Karnani, Neerja ;

Lee, Kirsten ;

Lefebvre, Gregory C. ;

Navas, Patrick A. ;

Neri, Fidencio ;

Parker, Stephen C. J. ;

Sabo, Peter J. ;

Sandstrom, Richard ;

Shafer, Anthony .

NATURE, 2007, 447 (7146) :799-816

[8]

Polycomb complexes repress developmental regulators in murine embryonic stem cells [J].

Boyer, LA ;

Plath, K ;

Zeitlinger, J ;

Brambrink, T ;

Medeiros, LA ;

Lee, TI ;

Levine, SS ;

Wernig, M ;

Tajonar, A ;

Ray, MK ;

Bell, GW ;

Otte, AP ;

Vidal, M ;

Gifford, DK ;

Young, RA ;

Jaenisch, R .

NATURE, 2006, 441 (7091) :349-353

[9]

Core transcriptional regulatory circuitry in human embryonic stem cells [J].

Boyer, LA ;

Lee, TI ;

Cole, MF ;

Johnstone, SE ;

Levine, SS ;

Zucker, JR ;

Guenther, MG ;

Kumar, RM ;

Murray, HL ;

Jenner, RG ;

Gifford, DK ;

Melton, DA ;

Jaenisch, R ;

Young, RA .

CELL, 2005, 122 (06) :947-956

[10]

Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions [J].

Bracken, AP ;

Dietrich, N ;

Pasini, D ;

Hansen, KH ;

Helin, K .

GENES & DEVELOPMENT, 2006, 20 (09) :1123-1136

← 1 2 3 4 5 6 →