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

Blood - Tập 122 - Trang 3165-3168 - 2013
Csaba Bödör1,2, Vera Grossmann3,4, Nikolay Popov1, Jessica Okosun1, Ciarán O'Riain1, King Tan5, Jacek Marzec6, Shamzah Araf1, Jun Wang6, Abigail M. Lee1, Andrew Clear1, Silvia Montoto1, Janet Matthews1, Sameena Iqbal1, Hajnalka Rajnai2, Andreas Rosenwald7, German Ott7,8, Elias Campo9, Lisa M. Rimsza10, Erlend B. Smeland11,12
1Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom;
2Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
3MLL Munich Leukemia Laboratory GmbH, Munich, Germany
4Center for Thrombosis and Hemostasis, University Medical Center Mainz, Johannes Gutenberg University, Mainz, Germany
5Department of Pathology, British Columbia Cancer Centre, Vancouver, BC, Canada;
6Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
7Institute of Pathology, University of Würzburg, Würzburg, Germany
8Department of Clinical Pathology, and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany;
9Department of Pathology, Hospital Clinic, University of Barcelona, Barcelona, Spain
10Department of Pathology, University of Arizona Cancer Centre, Tucson, AZ;
11Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
12Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway

Tóm tắt

Key Points EZH2 mutations occur in more than 25% of follicular lymphoma patients. Mutations predominantly represent an early/clonal event in the pathogenesis of the disease.

Tài liệu tham khảo

Pasqualucci, 2011, Inactivating mutations of acetyltransferase genes in B-cell lymphoma., Nature, 471, 189, 10.1038/nature09730 Morin, 2011, Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma., Nature, 476, 298, 10.1038/nature10351 Viré, 2006, The Polycomb group protein EZH2 directly controls DNA methylation., Nature, 439, 871, 10.1038/nature04431 Bödör, 2011, EZH2 Y641 mutations in follicular lymphoma., Leukemia, 25, 726, 10.1038/leu.2010.311 Morin, 2010, Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin., Nat Genet, 42, 181, 10.1038/ng.518 Sneeringer, 2010, Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas., Proc Natl Acad Sci USA, 107, 20980, 10.1073/pnas.1012525107 Yap, 2011, Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation., Blood, 117, 2451, 10.1182/blood-2010-11-321208 Ryan, 2011, EZH2 codon 641 mutations are common in BCL2-rearranged germinal center B cell lymphomas., PLoS ONE, 6, e28585, 10.1371/journal.pone.0028585 Lohr, 2012, Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing., Proc Natl Acad Sci USA, 109, 3879, 10.1073/pnas.1121343109 Majer, 2012, A687V EZH2 is a gain-of-function mutation found in lymphoma patients., FEBS Lett, 586, 3448, 10.1016/j.febslet.2012.07.066 McCabe, 2012, Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27)., Proc Natl Acad Sci USA, 109, 2989, 10.1073/pnas.1116418109 Creasy, 2012, A novel selective EZH2 inhibitor exhibits anti-tumor activity in lymphoma with EZH2 activating mutations., Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research, March 31-April 4, 2012, 492 McCabe, 2012, EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations., Nature, 492, 108, 10.1038/nature11606 Qi, 2012, Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation., Proc Natl Acad Sci USA, 109, 21360, 10.1073/pnas.1210371110 Dave, 2004, Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells., N Engl J Med, 351, 2159, 10.1056/NEJMoa041869 Grossmann, 2011, Molecular profiling of chronic myelomonocytic leukemia reveals diverse mutations in >80% of patients with TET2 and EZH2 being of high prognostic relevance., Leukemia, 25, 877, 10.1038/leu.2011.10 Kohlmann, 2011, The Interlaboratory RObustness of Next-generation sequencing (IRON) study: a deep sequencing investigation of TET2, CBL and KRAS mutations by an international consortium involving 10 laboratories., Leukemia, 25, 1840, 10.1038/leu.2011.155 Bachmann, 2005, Mutation screen and association study of EZH2 as a susceptibility gene for aggressive prostate cancer., Prostate, 65, 252, 10.1002/pros.20296 Van Loo, 2012, Analyzing cancer samples with SNP arrays., Methods Mol Biol, 802, 57, 10.1007/978-1-61779-400-1_4 Wrench, 2010, TNFRSF14 and EZH2 mutations, Chr2p gain and copy number changes targeting genes whose proteins interact with the microenvironment., Transformed follicular lymphoma Cheung, 2010, Acquired TNFRSF14 mutations in follicular lymphoma are associated with worse prognosis., Cancer Res, 70, 9166, 10.1158/0008-5472.CAN-10-2460 O’Shea, 2009, Regions of acquired uniparental disomy at diagnosis of follicular lymphoma are associated with both overall survival and risk of transformation., Blood, 113, 2298, 10.1182/blood-2008-08-174953 O’Riain, 2009, Array-based DNA methylation profiling in follicular lymphoma., Leukemia, 23, 1858, 10.1038/leu.2009.114 Green, 2013, Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma., Blood, 121, 1604, 10.1182/blood-2012-09-457283