Gene affected:
EZH2 - Enhancer of zeste 2 polycomb repressive complex 2 subunit (NM_004456.4)

Clinical significance
There is evidence that different mutations affecting EZH2 may confer adverse outcome either in MDS/MPN or in particular lymphoma types. At this time there is no specific clinical action indicated by the presence of this mutation, however EZH2 inhibitors are undergoing evaluation.

Function of gene

The protein encoded by the EZH2 gene functions as a histone methyltransferase belonging to the polycomb-group family which suppress gene transcription, promoting pluripotency and self-renewal. The genes have widespread cellular expression, but in haematology EZH2 mutations are associated with MPD/MDS and with lymphoma.

  • EZH2 mutations involving gene deletion or translocation are assumed to cause loss of function allowing the target genes of EZH2 to be expressed. These mutations are described predominantly in MDS and MPN disorders.
  • EZH2 mutations involving particular regions may cause gain of function, these mutations are also important, but in this case are associated with the development of specific lymphoma types.

NGS panel gene coverage

Loss of function monoallelic and biallelic mutations found in EZH2 include missense, nonsense, frameshift and splice site mutations. In addition to EZH2 mutation, decreased EZH2 expression can also be due to hemizygous deletions (7/del7q) removing the EZH2 gene. The panel is designed to detect all mutations affecting the essential regions of this gene.


Loss of function EZH2 mutations:
MDS/MPN disorders - CMML, atypical chronic myelogenous leukaemia (around 10-15% of cases); and myelofibrosis (around 15% of cases); but are also found in T-ALL.
Gain of function EZH2 mutations
Particular association with specific lymphoma types - Germinal Centre B-cell DLBCL and follicular lymphoma.

Note The importance of EZH2 in haematology is also highlighted by the over-expression of normal EZH2 protein in chronic lymphoid leukaemia, high-risk MDS or AML arising from a pre-existing MDS. Over expression is particularly seen in lymphomas including Burkitt lymphomas (100%); grade 3 follicular lymphomas (>80%), and diffuse large B-cell lymphomas (>80%), as well as mantle cell and natural killer T-cell lymphomas.

Associated genetic features: Lesions affecting EZH2 may accompany mutations affecting another epigenetic regulator gene: ASXL1


GeneWiki link:
Gene Wiki entry for EZH2
1. General Background
2. Prognostic outcome in AML
3. Prognostic outcome in MDS