EZH2 (enhancer of zeste homolog 2) encodes the catalytic subunit of the polycomb repressive complex 2 and represses transcription of a number of tumor suppressor genes. Simple variants in EZH2 are seen in about 2% of all tumors, including 2-3% of skin cancers and colorectal cancers. EZH2 inhibitors are in clinical trials for multiple tumor types.