EZH2 mutations are frequent and represent an early event in follicular lymphoma.

TitleEZH2 mutations are frequent and represent an early event in follicular lymphoma.
Publication TypeJournal Article
Year of Publication2013
AuthorsBödör C, Grossmann V, Popov N, Okosun J, O'Riain C, Tan K, Marzec J, Araf S, Wang J, Lee AM, Clear A, Montoto S, Matthews J, Iqbal S, Rajnai H, Rosenwald A, Ott G, Campo E, Rimsza LM, Smeland EB, Chan WC, Braziel RM, Staudt LM, Wright G, T Lister A, Elemento O, Hills R, Gribben JG, Chelala C, Matolcsy A, Kohlmann A, Haferlach T, Gascoyne RD, Fitzgibbon J
Date Published2013 Oct 31
KeywordsBiomarkers, Tumor, Cohort Studies, CREB-Binding Protein, Disease Progression, DNA Mutational Analysis, Enhancer of Zeste Homolog 2 Protein, Gene Expression Profiling, Gene Frequency, Humans, Kaplan-Meier Estimate, Lymphoma, Follicular, MEF2 Transcription Factors, Mutation, Polycomb Repressive Complex 2, Receptors, Tumor Necrosis Factor, Member 14, Time Factors

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 = 366) and performed a longitudinal analysis of mutation during the disease progression from FL to transformed FL (tFL) (n = 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.

Alternate JournalBlood
PubMed ID24052547
PubMed Central IDPMC3814734
Grant List12008 / / Cancer Research UK / United Kingdom
G0700052 / / Medical Research Council / United Kingdom
U01 CA157581 / CA / NCI NIH HHS / United States
C15966/A15968 / / Cancer Research UK / United Kingdom