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

Zheng Zhou, Juehua Gao, Relja Popovic, Kristy Wolniak, Vamsi Parimi, Jane N. Winter, Jonathan D. Licht, Yi Hua Chen*

*Corresponding author for this work

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2895-2901
Number of pages7
JournalLeukemia and Lymphoma
Volume56
Issue number10
DOIs
StatePublished - Oct 3 2015

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Keywords

  • Lymphoid malignancies
  • histopathology
  • mutation detection

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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