A687V EZH2 is a gain-of-function mutation found in lymphoma patients

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• 作者：Christina R. Majer ; Lei Jin ; Margaret Porter Scott ; Sarah K. Knutson ; Kevin W. Kuntz ; Heike Keilhack ; Jesse J. Smith ; Mikel P. Moyer ; Victoria M. Richon ; Robert A. Copel ; Tim J. Wigle
• 关键词：DLBCL ; diffuse large B-cell lymphoma ; CPM ; counts per minute ; GCB ; germinal Center B-cell-like ; H3K27 ; histone H3 lysine 27 ; NHL ; non-Hogdkin lymphoma ; PKMT ; protein lysine methyltransferase ; PRC2 ; Polycomb Repressive Complex 2 ; SAM ; S-adenosylmethionine
• 刊名：FEBS Letters
• 出版年：2012
• 出版时间：21 September, 2012
• 年：2012
• 卷：586
• 期：19
• 页码：3448-3451
• 全文大小：447 K

文摘

Heterozygous point mutations at Y641 and A677 in the EZH2 SET domain are prevalent in about 10-24 % of Non-Hodgkin lymphomas (NHL). Previous studies indicate that these are gain-of-function mutations leading to the hypertrimethylation of H3K27. These EZH2 mutations may drive the proliferation of lymphoma and make EZH2 a molecular target for patients harboring these mutations. Here, another EZH2 SET domain point mutation, A687V, occurring in about 1-2 % of lymphoma patients, is also shown to be a gain-of-function mutation that greatly enhances its ability to perform dimethylation relative to wild-type EZH2 and is equally proficient at catalyzing trimethylation. We propose that A687V EZH2 also leads to hypertrimethylation of H3K27 and may thus be a driver mutation in NHL.