EZH2 and lymphoma: Lymphoma-associated mutations affecting EZH2 were initially reported to result in enzymatic loss-of-function based on in vitro studies which used unmodified histone tails as a substrate for modification by recombinant PRC2 complexes, but the most common variants have subsequently been shown to possess increased activity in trimethylation of H3K27 in the mono- or di-methylated state.