While EZH2 deletion suppresses the germinal center formation, in B-cell lymphomas, EZH2 gain-of-function in the SET domain, including changes in tyrosine 641, A677G or A687V, promotes alterations in the substrate-binding pocket, enhancing H3K27me3 and decreasing H3K27me2 [105,106,107,108,109]. Here, EZH2 is linked to B-cell non-Hodgkin lymphoma.