Table 2 Comparison of EZH2 mutations: Y646x, D664x, and R690x in relation to cancer and PRC2 activity.
EZH2 Y646x mutation | EZH2 D664x mutation | EZH2 R690x mutation | |
|---|---|---|---|
PRC2 activity | “Gain-of-function” | “Loss-of-function” | |
Occurrence | Diffuse large B-cell lymphoma (25%) | EZH2 mutations: 5.5% of all MDS cases, 2.9% of all AML cases | |
Follicular lymphoma (12%) | |||
Melanoma (1%) | |||
Mutation site | EZH2 SET domain, inside the catalytic pocket | EZH2 SET domain, SET-I a-helix motif | EZH2 SET domain, close to the SAL domain |
Mutation | Y646F/N/H/S/C | D664G/V/E/A/H | R690H/C/G/S |
Mechanism | Increased conversion of H3K27me2 to H3K27me3 | Reduce PRC2 activity | Reduce global levels of H3K27me2 and H3K27me3 |
Etc | Potential significance for the docking of EZH2 inhibitors | ||
