@article{fb091193e0b24347a6f2b16a45811057,
title = "EZH2 mutations are frequent and represent an early event in follicular lymphoma",
abstract = "Gain of function mutations in the H3K27 methyltransferase EZH2 represent a promising therapeutic target in germinal center lymphomas. In this study, we assessed the frequency and distribution of EZH2 mutations in a large cohort of patients with follicular lymphoma (FL) (n 5 366) and performed a longitudinal analysis of mutation during the disease progression from FL to transformed FL (tFL) (n 5 33). Mutations were detected at 3 recurrent mutation hot spots (Y646, A682, and A692) in 27% of FL cases with variant allele frequencies (VAF) ranging from 2% to 61%. By comparing VAF of EZH2 with other mutation targets (CREBBP, MLL2, TNFRSF14, and MEF2B), we were able to distinguish patients harboring clonal EZH2 mutation from rarer cases with subclonal mutations. Overall, the high incidence of EZH2 mutations in FL and their stability during disease progression makes FL an appropriate disease to evaluate EZH2 targeted therapy.",
author = "Csaba B{\"o}d{\"o}r and Vera Grossmann and Nikolay Popov and Jessica Okosun and Ciar{\'a}n O{\textquoteright}Riain and King Tan and Jacek Marzec and Shamzah Araf and Jun Wang and Lee, {Abigail M.} and Andrew Clear and Silvia Montoto and Janet Matthews and Sameena Iqbal and Hajnalka Rajnai and Andreas Rosenwald and German Ott and Elias Campo and Rimsza, {Lisa M.} and Smeland, {Erlend B.} and Chan, {Wing C.} and Braziel, {Rita M.} and Staudt, {Louis M.} and George Wright and Lister, {T. Andrew} and Olivier Elemento and Robert Hills and Gribben, {John G.} and Claude Chelala and Andr{\'a}s Matolcsy and Alexander Kohlmann and Torsten Haferlach and Gascoyne, {Randy D.} and Fitzgibbon Jude",
note = "Funding Information: This work was supported by the Leukaemia Lymphoma Research UK (10036; J.F.), Partner fellowship (2009/01; C.B.) awarded by European Hematology Association, Kay Kendall Leukaemia Fund Junior Clinical Research Fellowship (KKL 557; J.O.), OTKA Funding Information: This work was supported by the Leukaemia Lymphoma Research UK (10036; J.F.), Partner fellowship (2009/01; C.B.) awarded by European Hematology Association, Kay Kendall Leukaemia Fund Junior Clinical Research Fellowship (KKL 557; J.O.), OTKA K-76204 grant (C.B. and A.M.), and Cancer Research UK Programme award (C15966/A15968; J.F.). C.B. was supported by the European Union and the State of Hungary, cofinanced by the European Social Fund in the framework of T?MOP 4.2.4. A/-11-1-2012-0001 National Excellence Program. Publisher Copyright: {\textcopyright} 2013, American Society of Hematology. All rights reserved ",
year = "2013",
doi = "10.1182/blood-2013-04-496893",
language = "English (US)",
volume = "122",
pages = "3165--3168",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "18",
}