title: Strong expression of EZH2 and accumulation of trimethylated H3K27 in diffuse large B-cell lymphoma independent of cell of origin and EZH2 codon 641 mutation.
abstract: Gain-of-function EZH2 mutation promotes H3K27 trimethylation (H3K27me3) and lymphoid transformation of germinal center (GC) derived B-cell lymphoma, such as GCB diffuse large B-cell lymphoma (DLBCL), but not activated B-cell (ABC) DLBCL. It is unclear whether expression levels of EZH2 and consequential H3K27me3 vary by EZH2 mutation and/or cell-of-origin in DLBCL. Ninety lymphoma samples including 40 DLBCLs were studied by immunohistochemistry. EZH2 Y641 mutations were detected in three of 20 (15%) GCB and none of 20 ABC types. All 40 DLBCLs showed strong EZH2, expression with high-level H3K27me3 in 90% GCBs and 95% ABCs. In 50 other B-cell lymphomas except for follicular lymphoma, strong EZH2 expression correlated with high-grade features. Immunoblot of DLBCL cell lines and microarray gene expression study of EZH2 in B-cell lymphomas were consistent with the immunohistochemistry findings. High-level EZH2 and H3K27me3 were common in DLBCL independent of cell-of-origin and EZH2 mutation. High-level EZH2 in lymphoma of aggressive features suggests additional therapeutic targets.
authors: a Division of Hematology and Oncology, Department of Medicine , Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine , Chicago , IL , USA.
authors: Zheng
authors: Z
authors: Zhou
authors: b Department of Pathology , Northwestern University Feinberg School of Medicine , Chicago , IL , USA.
authors: Juehua
authors: J
authors: Gao
authors: a Division of Hematology and Oncology, Department of Medicine , Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine , Chicago , IL , USA.
authors: Relja
authors: R
authors: Popovic
authors: b Department of Pathology , Northwestern University Feinberg School of Medicine , Chicago , IL , USA.
authors: Kristy
authors: K
authors: Wolniak
authors: b Department of Pathology , Northwestern University Feinberg School of Medicine , Chicago , IL , USA.
authors: Vamsi
authors: V
authors: Parimi
authors: a Division of Hematology and Oncology, Department of Medicine , Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine , Chicago , IL , USA.
authors: Jane N
authors: JN
authors: Winter
authors: a Division of Hematology and Oncology, Department of Medicine , Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine , Chicago , IL , USA.
authors: Jonathan D
authors: JD
authors: Licht
authors: b Department of Pathology , Northwestern University Feinberg School of Medicine , Chicago , IL , USA.
authors: Yi-Hua
authors: YH
authors: Chen
mesh_terms: D045744:Cell Line, Tumor; D003062:Codon; D019295:Computational Biology / Q000379:methods; D004252:DNA Mutational Analysis; D066264:Datasets as Topic; D018450:Disease Progression; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008745:Methylation; D009154:Mutation; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D003062:Codon; D006657:Histones; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
keywords: Lymphoid malignancies; histopathology; mutation detection