Gene

EZH2

enhancer of zeste 2 polycomb repressive complex 2 subunit

Explore in graph →CI-GENE-00001160HGNC:3527 ENSG00000106462 NCBI 2146 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (63)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–50 of 63 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
BRAF V600E + EZH2 Y646FEZH2 BRAF1
JQEZ5	Melanoma	Predictive	D	Supports Sensitivity Response	4

Cohorts

Alteration frequency by cohort (90)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved90 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Non-Hodgkin Lymphoma (BCGSC, Nature 2011) nhl_bcgsc_2011	Non-Hodgkin Lymphoma	Ssm	4

Literature

Linked publications (18)

25 per page, newest first.

pubmedPublishedShowing 1–18 of 18 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial.
· Lancet Oncol · 2020 · PMID 33035457 · validated civic_curation pubmed
Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study.
· Lancet Oncol · 2018 · PMID 29650362 · validated civic_curation pubmed
Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin.
· Nat Genet · 2010 · PMID 20081860 · validated civic_curation pubmed
An EZH2 polymorphism is associated with clinical outcome in metastatic colorectal cancer patients.
· Ann Oncol · 2012 · PMID 21926398 · validated

EZH2 A682G4
(oncogenic)	Follicular Lymphoma	Oncogenic	B	Supports Oncogenicity	3	accepted	EID12876 In this 2013 study, the authors analyzed 366 follicular lymphoma (FL) patients with additional paired samples from 33 cases of transformed FL. Patients harbored EZH2 mutations predominantly at codons … (full text at CIViC) PMID 24052547 · Bödör et al., 2013 · Open in CIViC	civic
〃	Follicular Lymphoma	Oncogenic	C	Supports Oncogenicity	3	accepted	EID12875 In this 2020 study, the authors analyzed four cases of follicular lymphoma using circulating tumor DNA and droplet digital PCR to monitor EZH2 hotspot mutations, including A682G. One patient with tran… (full text at CIViC) PMID 32668764 · Nagy et al., 2020 · Open in CIViC	civic
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	3	accepted	EID12408 The study demonstrates that EZH2 A677G is a gain-of-function mutation in B-cell lymphoma. In enzymatic assays, A677G uniquely utilized unmethylated, monomethylated, and dimethylated substrates with ne… (full text at CIViC) PMID 22323599 · McCabe et al., 2012 · Open in CIViC	civic
Tazemetostat	Non-Hodgkin Lymphoma	Predictive	D	Supports Sensitivity Response	3	submitted	EID12877 This 2014 preclinical study evaluated the EZH2 inhibitor EPZ-6438 (tazemetostat) in multiple EZH2-mutant non-Hodgkin lymphoma models, including the Pfeiffer lymphoma cell line harboring the EZH2 A682G… (full text at CIViC) PMID 24563539 · Knutson et al., 2014 · Open in CIViC	civic

EZH2 A682G4

(oncogenic)

Follicular Lymphoma

Oncogenic

Supports Oncogenicity

accepted

EID12876

In this 2013 study, the authors analyzed 366 follicular lymphoma (FL) patients with additional paired samples from 33 cases of transformed FL. Patients harbored EZH2 mutations predominantly at codons … (full text at CIViC)

PMID 24052547 · Bödör et al., 2013 · Open in CIViC

EZH2 Mutation3
(prognostic)	Follicular Lymphoma	Prognostic	B	Supports Better Outcome	4	accepted	EID1015 In advanced stage follicular lymphoma patients receiving rituximab + chemotherapy (R-CHOP or R-CVP), EZH2 mutations were associated with better failure free survival in patients with high-risk FLIPI s… (full text at CIViC) PMID 26256760 · Pastore et al., 2015 · Open in CIViC	civic
〃	Myelodysplastic SyndromeCURATED_BROADER	Prognostic	B	Supports Poor Outcome	3	accepted	EID425 In myelodysplastic syndrome, patients with point mutations in EZH2 have worse overall survival that their wild-type counterparts. PMID 20601954 · Nikoloski et al., 2010 · Open in CIViC	civic
〃	Myelodysplastic SyndromeCURATED_BROADER	Prognostic	B	Supports Poor Outcome	2	submitted	EID6945 In a study of 439 patients with myelodysplastic syndrome, patients with EZH2 mutations (N=10) has worse overall survival than wildtype patients (N=429) (P=0.02 univariate). This difference was also ob… (full text at CIViC) PMID 21714648 · Bejar et al., 2011 · Open in CIViC	civic

EZH2 Overexpression3
(prognostic)	Malignant NeoplasmALIAS	Prognostic	B	Supports Poor Outcome	4	accepted	EID731 High expression of EZH2 was associated with poorer outcome in a meta-analysis encompassing 51 studies and 9444 patients. PMID 26683709 · Jiang et al., 2016 · Open in CIViC	civic
〃	GlioblastomaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	2	submitted	EID8006 Kaplan-Meier analysis of EZH2 gene expression showed that elevated expression is significantly associated with shorter disease-free survival in GBM (p=1.3e-12). PMID 32180229 · Li et al., 2020 · Open in CIViC	civic
GSK126 + TazemetostatSequential	Neuroblastoma	Predictive	D	Supports Sensitivity Response	2	submitted	EID9115 Within this preclinical study, 87 patients with neuroblastoma and 14 neuroblastoma cell lines were evaluated for overexpression of EZH2 and possible prognostic factors. In patient samples the average … (full text at CIViC) PMID 28214660 · Bate-Eya et al., 2017 · Open in CIViC	civic

EZH2 Y6465
(diagnostic)	Diffuse Large B-Cell LymphomaCURATED_BROADER	Diagnostic	B	Supports Positive	4	accepted	EID432 Heterozygous mutations in EZH2 at Y641 were the second most frequent genetic event (after BCL2 t(14;18)) associated with a diagnosis of GCB-DLBCL in 35 / 320 patient samples. In contrast, mutations in… (full text at CIViC) PMID 20081860 · Morin et al., 2010 · Open in CIViC	civic
〃	Follicular Lymphoma	Diagnostic	B	Supports Positive	4	accepted	EID433 Heterozygous mutations in EZH2 at Y641 were the second most frequent genetic event (after BCL2 t(14;18)) associated with a diagnosis of Follicular non-Hodgkin Lymphoma in 18 / 251 patient samples. In … (full text at CIViC) PMID 20081860 · Morin et al., 2010 · Open in CIViC	civic
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	3	accepted	EID9412 Using a baculovirus expression system, wild-type EZH2 or Y641 (Y641F, Y641H, Y641N, Y641S) mutants were coexpressed with the PRC2 complex in Spodoptera frugiperda cells. Methyltransferase activity ass… (full text at CIViC) PMID 21078963 · Sneeringer et al., 2010 · Open in CIViC	civic
GSK126	Cutaneous MelanomaALIAS	Predictive	D	Supports Sensitivity Response	2	accepted	EID1494 Preclinical study in melanoma cell lines. EZH2 expression was higher in EZH2 mutant (N=3) and wild-type melanoma cell lines (N=12) than untransformed cells (human epithelial melanocytes and human derm… (full text at CIViC) PMID 26304929 · Tiffen et al., 2015 · Open in CIViC	civic
Dabrafenib + GSK126 + JQEZ5 + UNC1999Combination	Melanoma	Predictive	D	Supports Sensitivity Response	5	rejected	EID5677 Additional diseases: GC-DLBCL, Follicular lymphoma (FL). Y641 mutations are present in about 20% of GC-DLBCL, 10% FL, and 5% Melanoma (from TCGA/cBioportal). Also note that Y641 and Y646 mutations ar… (full text at CIViC) PMID 27135738 · Souroullas et al., 2016 · Open in CIViC	civic