Premium
A687V EZH2 is a gain‐of‐function mutation found in lymphoma patients
Author(s) -
Majer Christina R.,
Jin Lei,
Scott Margaret Porter,
Knutson Sarah K.,
Kuntz Kevin W.,
Keilhack Heike,
Smith Jesse J.,
Moyer Mikel P.,
Richon Victoria M.,
Copeland Robert A.,
Wigle Tim J.
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.07.066
Subject(s) - gain of function , ezh2 , mutation , cancer research , function (biology) , chemistry , lymphoma , medicine , biology , genetics , biochemistry , dna , methylation , gene
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.