EZH2 mutations are frequent and represent an early event in follicular lymphoma
| Autor: | Andreas Rosenwald, Erlend B. Smeland, T. Andrew Lister, Sameena Iqbal, Vera Grossmann, John G. Gribben, Alexander Kohlmann, George E. Wright, Lisa M. Rimsza, Claude Chelala, Nikolay Popov, German Ott, Robert Kerrin Hills, Randy D. Gascoyne, Andrew Clear, King Tan, Abigail M. Lee, Hajnalka Rajnai, Olivier Elemento, Wing C. Chan, Louis M. Staudt, Shamzah Araf, Ciaran O'Riain, Jessica Okosun, Rita M. Braziel, Janet Matthews, Torsten Haferlach, Jun Wang, Jacek Marzec, Elias Campo, András Matolcsy, Jude Fitzgibbon, Silvia Montoto, Csaba Bödör |
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| Rok vydání: | 2013 |
| Předmět: |
endocrine system
Time Factors Methyltransferase medicine.medical_treatment DNA Mutational Analysis Immunology Follicular lymphoma Kaplan-Meier Estimate macromolecular substances Biology medicine.disease_cause Biochemistry Targeted therapy Cohort Studies Gene Frequency hemic and lymphatic diseases Biomarkers Tumor medicine Humans Enhancer of Zeste Homolog 2 Protein Lymphoma Follicular Allele frequency Mutation Lymphoid Neoplasia MEF2 Transcription Factors Gene Expression Profiling EZH2 Polycomb Repressive Complex 2 Germinal center Cell Biology Hematology medicine.disease CREB-Binding Protein Lymphoma Disease Progression Cancer research Receptors Tumor Necrosis Factor Member 14 |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2013-04-496893 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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