@article{6830f055b1e243249ab8e964493992ea,
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.",
author = "Wendy B{\'e}guelin and Relja Popovic and Matt Teater and Yanwen Jiang and Bunting, {Karen L.} and Monica Rosen and Hao Shen and Yang, {Shao Ning} and Ling Wang and Teresa Ezponda and Eva Martinez-Garcia and Haikuo Zhang and Yupeng Zheng and Verma, {Sharad K.} and McCabe, {Michael T.} and Ott, {Heidi M.} and VanAller, {Glenn S.} and Kruger, {Ryan G.} and Yan Liu and McHugh, {Charles F.} and Scott, {David W.} and Chung, {Young Rock} and Neil Kelleher and Rita Shaknovich and Creasy, {Caretha L.} and Gascoyne, {Randy D.} and Wong, {Kwok Kin} and Leandro Cerchietti and Levine, {Ross L.} and Omar Abdel-Wahab and Licht, {Jonathan D.} and Olivier Elemento and Melnick, {Ari M.}",
note = "Funding Information: We thank Dr. Alexander Tarakhovsky (Rockefeller University) for sharing the EZH2 conditional knockout mouse strain. A.M.M. is supported by the Burroughs Wellcome Foundation and Chemotherapy Foundation. A.M.M., R.L.L., and J.D.L. are supported by the Samuel Waxman Cancer Research Foundation and a collaborative transnetwork grant from the National Cancer Institute Physical Sciences in Oncology Center program (U54 CA143869 and CA143879). J.D.L., A.M.M., and O.E. are supported by a Leukemia and Lymphoma Society Specialized Center of Research Excellence, and A.M.M. and J.D.L. are supported by the T & C Schwartz Family Foundation. O.A.-W. is an American Society of Hematology Basic Research Fellow and is supported by a grant from the NIH K08 Clinical Investigator Award (1K08CA160647-01). L.C. is a Raymond and Beverly Sackler Scholar and Scholar of the American Society of Hematology. D.W.S. is supported by a CIHR postdoctoral fellowship award, and R.D.G. is supported by a New Frontiers in Cancer Terry Fox Program project grant (No. 019001). O.E. and A.M.M. are supported by NCI R01 CA104348. O.E. is supported by the NSF CAREER grant and grants from the Starr Cancer Consortium. This work was enabled by the Beverly and Raymond Sackler Center for Physical and Biomedical Sciences as well as the Weill Cornell Epigenomics Core Facility. S.K.V., M.T.M., H.M.O., G.S.V.A., R.G.K., Y.L., C.F.M., and C.L.C. are employees of GlaxoSmithKline. ",
year = "2013",
month = may,
day = "13",
doi = "10.1016/j.ccr.2013.04.011",
language = "English (US)",
volume = "23",
pages = "677--692",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "5",
}