6533b7d0fe1ef96bd125a3bd
RESEARCH PRODUCT
EZH2 mutations are frequent and represent an early event in follicular lymphoma
Andreas RosenwaldErlend B. SmelandErlend B. SmelandT. Andrew ListerSameena IqbalVera GrossmannJohn G. GribbenAlexander KohlmannGeorge E. WrightLisa M. RimszaClaude ChelalaNikolay PopovGerman OttGerman OttRobert Kerrin HillsRandy D. GascoyneAndrew ClearKing TanAbigail M. LeeHajnalka RajnaiOlivier ElementoWing C. ChanLouis M. StaudtShamzah ArafCiaran O'riainJessica OkosunRita M. BrazielJanet MatthewsTorsten HaferlachJun WangJacek MarzecElias CampoAndrás MatolcsyJude FitzgibbonSilvia MontotoCsaba BödörCsaba Bödörsubject
endocrine systemTime FactorsMethyltransferasemedicine.medical_treatmentDNA Mutational AnalysisImmunologyFollicular lymphomaKaplan-Meier Estimatemacromolecular substancesBiologymedicine.disease_causeBiochemistryTargeted therapyCohort StudiesGene Frequencyhemic and lymphatic diseasesBiomarkers TumormedicineHumansEnhancer of Zeste Homolog 2 ProteinLymphoma FollicularAllele frequencyMutationLymphoid NeoplasiaMEF2 Transcription FactorsGene Expression ProfilingEZH2Polycomb Repressive Complex 2Germinal centerCell BiologyHematologymedicine.diseaseCREB-Binding ProteinLymphomaMutationDisease ProgressionCancer researchReceptors Tumor Necrosis Factor Member 14description
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-10-31 | Blood |