EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation Journal Article

   

Authors:	Béguelin, W.; Popovic, R.; Teater, M.; Jiang, Y.; Bunting, K.; Rosen, M.; Shen, H.; Yang, S.; Wang, L.; Ezponda, T.; Martinez-Garcia, E.; Zhang, H.; Zheng, Y.; Verma, S.; McCabe, M.; Ott, H.; VanAller, G.; Kruger, R.; Liu, Y.; McHugh, C.; Scott, D.; Chung, Y.; Kelleher, N.; Shaknovich, R.; Creasy, C.; Gascoyne, R.; Wong, K. K.; Cerchietti, L.; Levine, R.; Abdel-Wahab, O.; Licht, J.; Elemento, O.; Melnick, A.
Article Title:	EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation
Abstract:	The EZH2 histone methyltransferase is highly expressed in germinal center (GC) B cells and targeted by somatic mutations in B cell lymphomas. Here, we find that EZH2 deletion or pharmacologic inhibition suppresses GC formation and functions. EZH2 represses proliferation checkpoint genes and helps establish bivalent chromatin domains at key regulatory loci to transiently suppress GC B cell differentiation. Somatic mutations reinforce these physiological effects through enhanced silencing of EZH2 targets. Conditional expression of mutant EZH2 in mice induces GC hyperplasia and accelerated lymphomagenesis in cooperation with BCL2. GC B cell (GCB)-type diffuse large B cell lymphomas (DLBCLs) are mostly addicted to EZH2 but not the more differentiated activated B cell (ABC)-type DLBCLs, thus clarifying the therapeutic scope of EZH2 targeting. © 2013 Elsevier Inc.
Journal Title:	Cancer Cell
Volume:	23
Issue:	5
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2013-05-13
Start Page:	677
End Page:	692
Language:	English
DOI:	10.1016/j.ccr.2013.04.011
PROVIDER:	scopus
PUBMED:	23680150
PMCID:	PMC3681809
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84877815031&partnerID=40&md5=100f8d972af101e7342d142f0144bac9
Notes:	--- - Cited By (since 1996):1 - "Export Date: 3 June 2013" - "CODEN: CCAEC" - "Source: Scopus"

https://synapse.mskcc.org/synapse/works/has_related_data_chk/41182